5-90745274-A-G

Position:

chr5-90745274-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032119.4(ADGRV1):c.10769+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00788 in 1,540,212 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0080 ( 45 hom. )

Consequence

ADGRV1
NM_032119.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.387

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 5-90745274-A-G is Benign according to our data. Variant chr5-90745274-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 46251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90745274-A-G is described in Lovd as [Benign]. Variant chr5-90745274-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0063 (959/152284) while in subpopulation AMR AF= 0.0105 (161/15294). AF 95% confidence interval is 0.0092. There are 6 homozygotes in gnomad4. There are 446 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.10769+9A>G		intron_variant		ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.10769+9A>G		intron_variant		1	NM_032119.4	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.00630

AC:

959

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00882

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00685

AC:

1472

AN:

214876

Hom.:

AF XY:

0.00705

AC XY:

828

AN XY:

117422

show subpopulations

Gnomad AFR exome

AF:

0.000807

Gnomad AMR exome

AF:

0.00583

Gnomad ASJ exome

AF:

0.0308

Gnomad EAS exome

AF:

0.0000604

Gnomad SAS exome

AF:

0.00194

Gnomad FIN exome

AF:

0.00254

Gnomad NFE exome

AF:

0.00903

Gnomad OTH exome

AF:

0.00469

GnomAD4 exome

AF:

0.00805

AC:

11171

AN:

1387928

Hom.:

Cov.:

AF XY:

0.00801

AC XY:

5517

AN XY:

689056

show subpopulations

Gnomad4 AFR exome

AF:

0.000957

Gnomad4 AMR exome

AF:

0.00582

Gnomad4 ASJ exome

AF:

0.0252

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00225

Gnomad4 FIN exome

AF:

0.00301

Gnomad4 NFE exome

AF:

0.00886

Gnomad4 OTH exome

AF:

0.00850

GnomAD4 genome

AF:

0.00630

AC:

959

AN:

152284

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

446

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00882

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00648

Hom.:

Bravo

AF:

0.00645

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:7

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 02, 2017	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	ADGRV1: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 09, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 26, 2012	10769+9A>G in intron 51 of GPR98: This variant is not expected to have clinical significance because it has been identified in 82/6550 (1.25%) European American chromosomes from a broad, though clinically unspecified population (NHLBI Exom e Sequencing Project; http://evs.gs.washington.edu/EVS; rs116184119). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

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

-0.78

CADD

Benign

2.1

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over