rs2438358

Positions:

• chr5-90783117-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000405460.9(ADGRV1):​c.13232-7A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00535 in 1,611,722 control chromosomes in the GnomAD database, including 371 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (184 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (187 hom.)
• Consequence: ADGRV1 ENST00000405460.9 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001466
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.13

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 5-90783117-A-G is Benign according to our data. Variant chr5-90783117-A-G is described in ClinVar as [Benign]. Clinvar id is 46266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90783117-A-G is described in Lovd as [Likely_benign]. Variant chr5-90783117-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.13232-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.13232-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032119.4	ENSP00000384582	P1
ADGRV1	ENST00000638510.1	n.499-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
ADGRV1	ENST00000425867.3	c.2186-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000392618
ADGRV1	ENST00000639431.1	c.265+106908A>G		intron_variant, NMD_transcript_variant		5		ENSP00000491057

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4308 AN: 152094 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0974

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.00726 AC: 1805 AN: 248558 Hom.: 80 AF XY: 0.00550 AC XY: 742 AN XY: 134812

Gnomad AFR exome AF: 0.0994

Gnomad AMR exome AF: 0.00525

Gnomad ASJ exome AF: 0.000498

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000373

Gnomad OTH exome AF: 0.00515

GnomAD4 exome AF: 0.00295 AC: 4307 AN: 1459510 Hom.: 187 Cov.: 30 AF XY: 0.00253 AC XY: 1836 AN XY: 725982

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.00555

Gnomad4 ASJ exome AF: 0.000498

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000224

Gnomad4 OTH exome AF: 0.00644

GnomAD4 genome AF: 0.0283 AC: 4315 AN: 152212 Hom.: 184 Cov.: 32 AF XY: 0.0272 AC XY: 2022 AN XY: 74414

Gnomad4 AFR AF: 0.0973

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0228

Alfa AF: 0.0122 Hom.: 50

Bravo AF: 0.0317

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 04, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	13232-7A>G in Intron 65 of GPR98: This variant is not expected to have clinical significance because it has been identified in 9.0% (296/3300) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs2438358). -
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:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 16, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.2
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
SpliceAI score (max)		0.030		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: rs2438358; hg19: chr5-90078934;