5-90783994-C-T

Position:

• chr5-90783994-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_032119.4(ADGRV1):​c.13590C>T​(p.Pro4530Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,612,110 control chromosomes in the GnomAD database, including 357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (32 hom., cov: 32)
  • Exomes 𝑓: 0.018 (325 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.209

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 5-90783994-C-T is Benign according to our data. Variant chr5-90783994-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 46267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90783994-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.209 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.015 (2276/152228) while in subpopulation NFE AF= 0.0224 (1523/68012). AF 95% confidence interval is 0.0215. There are 32 homozygotes in gnomad4. There are 1092 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.13590C>T	p.Pro4530Pro	synonymous_variant	67/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.13590C>T	p.Pro4530Pro	synonymous_variant	67/90	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2277 AN: 152110 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00721

Gnomad ASJ AF: 0.00895

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.0153 AC: 3781 AN: 246944 Hom.: 51 AF XY: 0.0153 AC XY: 2048 AN XY: 133900

Gnomad AFR exome AF: 0.00267

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.0116

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00377

Gnomad FIN exome AF: 0.0414

Gnomad NFE exome AF: 0.0217

Gnomad OTH exome AF: 0.0141

GnomAD4 exome AF: 0.0184 AC: 26857 AN: 1459882 Hom.: 325 Cov.: 31 AF XY: 0.0181 AC XY: 13158 AN XY: 726144

Gnomad4 AFR exome AF: 0.00233

Gnomad4 AMR exome AF: 0.00375

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00386

Gnomad4 FIN exome AF: 0.0433

Gnomad4 NFE exome AF: 0.0205

Gnomad4 OTH exome AF: 0.0140

GnomAD4 genome AF: 0.0150 AC: 2276 AN: 152228 Hom.: 32 Cov.: 32 AF XY: 0.0147 AC XY: 1092 AN XY: 74436

Gnomad4 AFR AF: 0.00344

Gnomad4 AMR AF: 0.00720

Gnomad4 ASJ AF: 0.00895

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0405

Gnomad4 NFE AF: 0.0224

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0161 Hom.: 12

Bravo AF: 0.0113

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 01, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2014	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. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 26, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 21, 2010	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Usher syndrome type 2C Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	5.7
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs41311745; hg19: chr5-90079811;