5-90725106-T-G

Position:

• chr5-90725106-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000405460.9(ADGRV1):​c.9927T>G​(p.Pro3309=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,533,190 control chromosomes in the GnomAD database, including 90,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8211 hom., cov: 32)
  • Exomes 𝑓: 0.34 (82065 hom.)
• Consequence: ADGRV1 ENST00000405460.9 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.0120

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]

LOC105379077 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 5-90725106-T-G is Benign according to our data. Variant chr5-90725106-T-G is described in ClinVar as [Benign]. Clinvar id is 46409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90725106-T-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.012 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.9927T>G	p.Pro3309=	synonymous_variant	47/90	ENST00000405460.9	NP_115495.3
LOC105379077	XR_001742802.2	n.364-9297A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.9927T>G	p.Pro3309=	synonymous_variant	47/90	1	NM_032119.4	ENSP00000384582	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48357 AN: 151878 Hom.: 8197 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.357

GnomAD3 exomes AF: 0.346 AC: 73643 AN: 212900 Hom.: 13608 AF XY: 0.342 AC XY: 39766 AN XY: 116402

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.367

Gnomad SAS exome AF: 0.315

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.340 AC: 469218 AN: 1381196 Hom.: 82065 Cov.: 27 AF XY: 0.338 AC XY: 233051 AN XY: 689078

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.551

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.436

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.318 AC: 48376 AN: 151994 Hom.: 8211 Cov.: 32 AF XY: 0.321 AC XY: 23862 AN XY: 74286

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.351

Alfa AF: 0.294 Hom.: 2956

Bravo AF: 0.333

Asia WGS AF: 0.339 AC: 1174 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 07, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 23, 2010	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Usher syndrome type 2C Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.8
DANN	Benign	0.66

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: rs16869042; hg19: chr5-90020923; COSMIC: COSV67980903;