rs2276020

Variant names:

• chr11-67490085-C-T
• rs2276020
• NM_003977.4:c.516C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-67490085-C-T
• chr11-67490085-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.88
• Publications: 18 publications found

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]

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIP	NM_003977.4	MANE Select	c.516C>T	p.Asp172Asp	synonymous	Exon 4 of 6	NP_003968.3	O00170
	AIP	NM_001302960.2		c.516C>T	p.Asp172Asp	synonymous	Exon 4 of 6	NP_001289889.1	A0A804HJ38
	AIP	NM_001302959.2		c.339C>T	p.Asp113Asp	synonymous	Exon 4 of 6	NP_001289888.1	A0A804HKL7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIP	ENST00000279146.8	TSL:1 MANE Select	c.516C>T	p.Asp172Asp	synonymous	Exon 4 of 6	ENSP00000279146.3	O00170
	AIP	ENST00000934218.1		c.606C>T	p.Asp202Asp	synonymous	Exon 4 of 6	ENSP00000604277.1
	AIP	ENST00000872352.1		c.516C>T	p.Asp172Asp	synonymous	Exon 4 of 6	ENSP00000542411.1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4941 AN: 152150 Hom.: 127 Cov.: 33

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

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.: 31 AF XY: 0.0212 AC XY: 15386 AN XY: 725752

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: 83 AN: 5764

European-Non Finnish (NFE) AF: 0.0116 AC: 12887 AN: 1111278

Other (OTH) AF: 0.0267 AC: 1611 AN: 60312

GnomAD4 genome AF: 0.0325 AC: 4955 AN: 152268 Hom.: 129 Cov.: 33 AF XY: 0.0352 AC XY: 2621 AN XY: 74432

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: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0141 AC: 956 AN: 68028

Other (OTH) AF: 0.0304 AC: 64 AN: 2106

Alfa AF: 0.0209 Hom.: 32

Bravo AF: 0.0305

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	2	Somatotroph adenoma (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.1
DANN	Benign	0.87
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2276020; hg19: chr11-67257556; COSMIC: COSV54159721; COSMIC: COSV54159721;