Variant 5-90756446-TC-TCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The NM_032119.4(ADGRV1):c.11581-3dupC variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,448,428 control chromosomes in the GnomAD database, including 128,976 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11886 hom., cov: 0)

Exomes 𝑓: 0.42 ( 117090 hom. )

Consequence

ADGRV1
NM_032119.4 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.401

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:

ADGRV1 (HGNC:):

ADGRV1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.009301834 fraction of the gene. Cryptic splice site detected, with MaxEntScore 11, offset of 0 (no position change), new splice context is: tttttcccccatccccccAGgat. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BP6

Variant 5-90756446-T-TC is Benign according to our data. Variant chr5-90756446-T-TC is described in ClinVar as [Benign]. Clinvar id is 46256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.11581-3dupC		splice_acceptor_variant, intron_variant		ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.11581-3dupC		splice_acceptor_variant, intron_variant		1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57640

AN:

151804

Hom.:

11878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.539

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.420

GnomAD3 exomes

AF:

0.402

AC:

73922

AN:

183724

Hom.:

16040

AF XY:

0.402

AC XY:

40810

AN XY:

101550

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.590

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.407

Gnomad SAS exome

AF:

0.345

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.417

AC:

540617

AN:

1296506

Hom.:

117090

Cov.:

AF XY:

0.414

AC XY:

263736

AN XY:

636982

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.578

Gnomad4 ASJ exome

AF:

0.319

Gnomad4 EAS exome

AF:

0.493

Gnomad4 SAS exome

AF:

0.330

Gnomad4 FIN exome

AF:

0.426

Gnomad4 NFE exome

AF:

0.424

Gnomad4 OTH exome

AF:

0.407

GnomAD4 genome

AF:

0.380

AC:

57664

AN:

151922

Hom.:

11886

Cov.:

AF XY:

0.383

AC XY:

28432

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.213

Gnomad4 AMR

AF:

0.540

Gnomad4 ASJ

AF:

0.338

Gnomad4 EAS

AF:

0.481

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.442

Gnomad4 NFE

AF:

0.429

Gnomad4 OTH

AF:

0.417

Alfa

AF:

0.363

Hom.:

1767

Bravo

AF:

0.382

Asia WGS

AF:

0.431

AC:

1498

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 08, 2012	11581-3_11581-2insC in intron 55 of GPR98: This variant is not expected to have clinical significance because it has been found frequently in the general popula tion (rs34894132 - 7 entries) and in 9/13 cases from our laboratory. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 22, 2015	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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