chr5-90558926-T-C

Position:

• chr5-90558926-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_032119.4(ADGRV1):​c.22+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000461 in 1,555,924 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (1 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.894

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 5-90558926-T-C is Benign according to our data. Variant chr5-90558926-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 193464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90558926-T-C is described in Lovd as [Benign]. Variant chr5-90558926-T-C is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd4 at 2 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.22+9T>C		intron_variant		ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.22+9T>C		intron_variant		1	NM_032119.4	ENSP00000384582	P1

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 339 AN: 152022 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00712

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000579 AC: 92 AN: 158876 Hom.: 1 AF XY: 0.000474 AC XY: 40 AN XY: 84320

Gnomad AFR exome AF: 0.00796

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.000587

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000431

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000962

Gnomad OTH exome AF: 0.000911

GnomAD4 exome AF: 0.000270 AC: 379 AN: 1403788 Hom.: 1 Cov.: 30 AF XY: 0.000254 AC XY: 176 AN XY: 692834

Gnomad4 AFR exome AF: 0.00698

Gnomad4 AMR exome AF: 0.000637

Gnomad4 ASJ exome AF: 0.000477

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000376

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000564

Gnomad4 OTH exome AF: 0.000791

GnomAD4 genome AF: 0.00223 AC: 339 AN: 152136 Hom.: 2 Cov.: 32 AF XY: 0.00214 AC XY: 159 AN XY: 74380

Gnomad4 AFR AF: 0.00710

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00150 Hom.: 0

Bravo AF: 0.00252

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 05, 2020	- -

not specified Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 04, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	c.22+9T>C in intron 01 of GPR98: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence and has been identified in 0.9% (18/2005) of African American chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs368604803). -

ADGRV1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 10, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.1
DANN	Benign	0.61

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: rs368604803; hg19: chr5-89854743;