Genetic Variant NM_001134831.2:c.*396_*397dupTG (chr6-135285247-C-CCA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001134831.2(AHI1):c.*396_*397dupTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 233,098 control chromosomes in the GnomAD database, including 1,712 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1578 hom., cov: 31)

Exomes 𝑓: 0.051 ( 134 hom. )

Consequence

AHI1
NM_001134831.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.592

Publications

0 publications found

Variant links:

Genes affected

AHI1 (HGNC:21575): (Abelson helper integration site 1) This gene is apparently required for both cerebellar and cortical development in humans. This gene mutations cause specific forms of Joubert syndrome-related disorders. Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

AHI1 Gene-Disease associations (from GenCC):

Joubert syndrome 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Laboratory for Molecular Medicine, Ambry Genetics
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with ocular defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet

AHI1 links:

ENSG00000234084 (HGNC:):

ENSG00000234084 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 6-135285247-C-CCA is Benign according to our data. Variant chr6-135285247-C-CCA is described in ClinVar as [Likely_benign]. Clinvar id is 355489.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2 link	c.396_397dupTG		3_prime_UTR_variant	Exon 29 of 29	ENST00000265602.11	NP_001128303.1	Q8N157-1Q8NER0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11 link	c.396_397dupTG		3_prime_UTR_variant	Exon 29 of 29	1	NM_001134831.2	ENSP00000265602.6		Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17642

AN:

152092

Hom.:

1567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0845

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.0673

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0243

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0666

Gnomad OTH

AF:

0.104

GnomAD4 exome

AF:

0.0507

AC:

4102

AN:

80888

Hom.:

134

Cov.:

AF XY:

0.0513

AC XY:

2172

AN XY:

42334

show subpopulations

African (AFR)

AF:

0.159

AC:

320

AN:

2012

American (AMR)

AF:

0.0646

AC:

275

AN:

4260

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

2232

East Asian (EAS)

AF:

0.0472

AC:

229

AN:

4850

South Asian (SAS)

AF:

0.0678

AC:

646

AN:

9522

European-Finnish (FIN)

AF:

0.0207

AC:

AN:

3574

Middle Eastern (MID)

AF:

0.0348

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0459

AC:

2274

AN:

49544

Other (OTH)

AF:

0.0498

AC:

228

AN:

4578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

155

310

465

620

775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.116

AC:

17693

AN:

152210

Hom.:

1578

Cov.:

AF XY:

0.112

AC XY:

8322

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.250

AC:

10363

AN:

41478

American (AMR)

AF:

0.0842

AC:

1288

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0245

AC:

AN:

3470

East Asian (EAS)

AF:

0.0672

AC:

349

AN:

5190

South Asian (SAS)

AF:

0.108

AC:

523

AN:

4832

European-Finnish (FIN)

AF:

0.0243

AC:

258

AN:

10612

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0666

AC:

4528

AN:

68020

Other (OTH)

AF:

0.110

AC:

233

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

762

1525

2287

3050

3812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0923

Hom.:

107

Bravo

AF:

0.125

Asia WGS

AF:

0.145

AC:

505

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Joubert syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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NM_001134831.2:c.396_397dupTG

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