rs377585302

Positions:

• chr5-90706404-T-TC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_032119.4(ADGRV1):​c.8730+10_8730+11insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 701,856 control chromosomes in the GnomAD database, including 82 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (33 hom., cov: 31)
  • Exomes 𝑓: 0.0044 (49 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.54

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 -16 ACMG points.

• BP6: Variant 5-90706404-T-TC is Benign according to our data. Variant chr5-90706404-T-TC is described in ClinVar as [Likely_benign]. Clinvar id is 46397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.8730+10_8730+11insC		intron_variant		ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.8730+10_8730+11insC		intron_variant		1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 1047 AN: 14892 Hom.: 31 Cov.: 31

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000690

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.00442 AC: 3037 AN: 686940 Hom.: 49 Cov.: 30 AF XY: 0.00406 AC XY: 1374 AN XY: 338096

Gnomad4 AFR exome AF: 0.00171

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0184

Gnomad4 SAS exome AF: 0.00135

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000655

Gnomad4 OTH exome AF: 0.00621

GnomAD4 genome AF: 0.0709 AC: 1057 AN: 14916 Hom.: 33 Cov.: 31 AF XY: 0.0813 AC XY: 592 AN XY: 7282

Gnomad4 AFR AF: 0.0631

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.0136

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000690

Gnomad4 OTH AF: 0.157

Alfa AF: 0.00556 Hom.: 2

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 02, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2018	- -

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 19, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 07, 2014	c.8730+10_8730+11insC in intron 38 of GPR98: This variant is not expected to hav e clinical significance because it has been identified in 4.2% (15/358) of Latin American (Puerto Rican, Mexican-American, Columbian) chromosomes and 2.4% (14/5 72) of East Asian (Chinese and Japanese) chromosomes by the 1000 Genomes Project (dbSNP rs377585302). -

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

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 28, 2022

- -

Computational scores

Source: dbNSFP v4.3

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: rs377585302; hg19: chr5-90002221;