5-90756555-C-T

Variant names:

• chr5-90756555-C-T
• rs2438349
• NM_032119.4:c.11682C>T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):​c.11682C>T​(p.Pro3894Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,610,038 control chromosomes in the GnomAD database, including 178,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21400 hom., cov: 31)
  • Exomes 𝑓: 0.46 (157159 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.842

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 5-90756555-C-T is Benign according to our data. Variant chr5-90756555-C-T is described in ClinVar as [Benign]. Clinvar id is 46258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90756555-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.842 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.11682C>T	p.Pro3894Pro	synonymous_variant	Exon 56 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.11682C>T	p.Pro3894Pro	synonymous_variant	Exon 56 of 90	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78972 AN: 151736 Hom.: 21360 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.519

GnomAD3 exomes AF: 0.487 AC: 121081 AN: 248730 Hom.: 30949 AF XY: 0.474 AC XY: 63913 AN XY: 134906

Gnomad AFR exome AF: 0.676

Gnomad AMR exome AF: 0.675

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.456

Gnomad SAS exome AF: 0.417

Gnomad FIN exome AF: 0.443

Gnomad NFE exome AF: 0.446

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.460 AC: 670601 AN: 1458184 Hom.: 157159 Cov.: 34 AF XY: 0.456 AC XY: 330690 AN XY: 725490

Gnomad4 AFR exome AF: 0.672

Gnomad4 AMR exome AF: 0.666

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.504

Gnomad4 SAS exome AF: 0.420

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.468

GnomAD4 genome AF: 0.521 AC: 79070 AN: 151854 Hom.: 21400 Cov.: 31 AF XY: 0.521 AC XY: 38671 AN XY: 74188

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.515

Alfa AF: 0.470 Hom.: 9394

Bravo AF: 0.543

Asia WGS AF: 0.477 AC: 1659 AN: 3478

EpiCase AF: 0.447

EpiControl AF: 0.446

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 29, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 22, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	1.8
DANN	Benign	0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2438349; hg19: chr5-90052372; COSMIC: COSV67980909; COSMIC: COSV67980909;