rs17624033

Variant names:

• chr5-90745693-A-G
• rs17624033
• NM_032119.4:c.10872A>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_032119.4(ADGRV1):​c.10872A>G​(p.Gln3624Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 1,612,324 control chromosomes in the GnomAD database, including 1,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (125 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1489 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: 0.128
• Publications: 7 publications found

Genes affected

ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

ADGRV1 Gene-Disease associations (from GenCC):

• Usher syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Usher syndrome type 2C

  Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• febrile seizures, familial, 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.066).
• BP6: Variant 5-90745693-A-G is Benign according to our data. Variant chr5-90745693-A-G is described in ClinVar as Benign. ClinVar VariationId is 46252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.128 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0318 (4840/152296) while in subpopulation AMR AF = 0.0466 (713/15294). AF 95% confidence interval is 0.0438. There are 125 homozygotes in GnomAd4. There are 2280 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 125 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.10872A>G	p.Gln3624Gln	synonymous_variant	Exon 52 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.10872A>G	p.Gln3624Gln	synonymous_variant	Exon 52 of 90	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4842 AN: 152178 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.00881

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0713

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.0502

GnomAD2 exomes AF: 0.0312 AC: 7750 AN: 248594 AF XY: 0.0317

Gnomad AFR exome AF: 0.00698

Gnomad AMR exome AF: 0.0272

Gnomad ASJ exome AF: 0.0623

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.0200

Gnomad NFE exome AF: 0.0434

Gnomad OTH exome AF: 0.0382

GnomAD4 exome AF: 0.0420 AC: 61301 AN: 1460028 Hom.: 1489 Cov.: 29 AF XY: 0.0413 AC XY: 30017 AN XY: 726416

African (AFR) AF: 0.00783 AC: 262 AN: 33456

American (AMR) AF: 0.0288 AC: 1287 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 1644 AN: 26122

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39644

South Asian (SAS) AF: 0.0177 AC: 1522 AN: 86230

European-Finnish (FIN) AF: 0.0217 AC: 1154 AN: 53164

Middle Eastern (MID) AF: 0.0472 AC: 271 AN: 5744

European-Non Finnish (NFE) AF: 0.0474 AC: 52673 AN: 1110634

Other (OTH) AF: 0.0412 AC: 2485 AN: 60320

GnomAD4 genome AF: 0.0318 AC: 4840 AN: 152296 Hom.: 125 Cov.: 32 AF XY: 0.0306 AC XY: 2280 AN XY: 74460

African (AFR) AF: 0.00878 AC: 365 AN: 41572

American (AMR) AF: 0.0466 AC: 713 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0713 AC: 247 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4818

European-Finnish (FIN) AF: 0.0187 AC: 199 AN: 10620

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0447 AC: 3041 AN: 68014

Other (OTH) AF: 0.0497 AC: 105 AN: 2112

Alfa AF: 0.0428 Hom.: 500

Bravo AF: 0.0344

Asia WGS AF: 0.00895 AC: 32 AN: 3478

EpiCase AF: 0.0477

EpiControl AF: 0.0463

ClinVar

Significance: Benign

Submissions summary: Benign:7 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Mar 20, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 14, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 11, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1 Other:1

-

NEI Ophthalmic Genomics Laboratory, National Institutes of Health

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 2C Benign:1

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.3
DANN	Benign	0.30
PhyloP100		0.13
PromoterAI		-0.0022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs17624033; hg19: chr5-90041510;