11-67490085-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003977.4(AIP):c.516C>T(p.Asp172Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 1,611,554 control chromosomes in the GnomAD database, including 1,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 129 hom., cov: 33)

Exomes 𝑓: 0.021 ( 904 hom. )

Consequence

AIP
NM_003977.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.88

Publications

18 publications found

Variant links:

Genes affected

AIP (HGNC:358): (aryl hydrocarbon receptor interacting protein) The protein encoded by this gene is a receptor for aryl hydrocarbons and a ligand-activated transcription factor. The encoded protein is found in the cytoplasm as part of a multiprotein complex, but upon binding of ligand is transported to the nucleus. This protein can regulate the expression of many xenobiotic metabolizing enzymes. Also, the encoded protein can bind specifically to and inhibit the activity of hepatitis B virus. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

AIP links:

MIR6752 (HGNC:50020): (microRNA 6752) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6752 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 11-67490085-C-T is Benign according to our data. Variant chr11-67490085-C-T is described in ClinVar as Benign. ClinVar VariationId is 305728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIP	NM_003977.4 link	c.516C>T	p.Asp172Asp	synonymous_variant	Exon 4 of 6	ENST00000279146.8	NP_003968.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIP	ENST00000279146.8 link	c.516C>T	p.Asp172Asp	synonymous_variant	Exon 4 of 6	1	NM_003977.4	ENSP00000279146.3

Frequencies

GnomAD3 genomes

AF:

0.0325

AC:

4941

AN:

152150

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0450

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0366

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0288

GnomAD2 exomes

AF:

0.0338

AC:

8325

AN:

245994

AF XY:

0.0328

show subpopulations

Gnomad AFR exome

AF:

0.0454

Gnomad AMR exome

AF:

0.0250

Gnomad ASJ exome

AF:

0.0272

Gnomad EAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.0632

Gnomad NFE exome

AF:

0.0145

Gnomad OTH exome

AF:

0.0274

GnomAD4 exome

AF:

0.0209

AC:

30542

AN:

1459286

Hom.:

904

Cov.:

AF XY:

0.0212

AC XY:

15386

AN XY:

725752

show subpopulations

African (AFR)

AF:

0.0477

AC:

1596

AN:

33450

American (AMR)

AF:

0.0265

AC:

1180

AN:

44472

Ashkenazi Jewish (ASJ)

AF:

0.0273

AC:

711

AN:

26090

East Asian (EAS)

AF:

0.157

AC:

6200

AN:

39616

South Asian (SAS)

AF:

0.0360

AC:

3089

AN:

85910

European-Finnish (FIN)

AF:

0.0608

AC:

3185

AN:

52394

Middle Eastern (MID)

AF:

0.0144

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0116

AC:

12887

AN:

1111278

Other (OTH)

AF:

0.0267

AC:

1611

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1892

3783

5675

7566

9458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

576

1152

1728

2304

2880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0325

AC:

4955

AN:

152268

Hom.:

129

Cov.:

AF XY:

0.0352

AC XY:

2621

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0451

AC:

1874

AN:

41544

American (AMR)

AF:

0.0245

AC:

375

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.0317

AC:

110

AN:

3472

East Asian (EAS)

AF:

0.126

AC:

653

AN:

5184

South Asian (SAS)

AF:

0.0363

AC:

175

AN:

4826

European-Finnish (FIN)

AF:

0.0706

AC:

747

AN:

10588

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0141

AC:

956

AN:

68028

Other (OTH)

AF:

0.0304

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

242

484

725

967

1209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0209

Hom.:

Bravo

AF:

0.0305

Asia WGS

AF:

0.0830

AC:

287

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Somatotroph adenoma

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hereditary cancer-predisposing syndrome

Benign:2

Aug 12, 2020

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Dec 13, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.1

(source)

DANN

Benign

0.87

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over