rs75881968

chr5-90706218-C-T

Variant summary

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

The NM_032119.4(ADGRV1):c.8567-13C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,582,704 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (140 hom.)
• Consequence: ADGRV1 NM_032119.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.712

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=-0.83).
• BP6: Variant 5-90706218-C-T is Benign according to our data. Variant chr5-90706218-C-T is described in ClinVar as [Benign]. Clinvar id is 46392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90706218-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.084 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4	c.8567-13C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.8567-13C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_032119.4	P1

Frequencies

GnomAD3 genomes AF: 0.00381 AC: 579 AN: 152054 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0903

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00767 AC: 1710 AN: 222830 Hom.: 68 AF XY: 0.00709 AC XY: 859 AN XY: 121166

Gnomad AFR exome AF: 0.000936

Gnomad AMR exome AF: 0.000149

Gnomad ASJ exome AF: 0.000244

Gnomad EAS exome AF: 0.0976

Gnomad SAS exome AF: 0.00152

Gnomad FIN exome AF: 0.00172

Gnomad NFE exome AF: 0.0000475

Gnomad OTH exome AF: 0.00189

GnomAD4 exome AF: 0.00264 AC: 3770 AN: 1430532 Hom.: 140 Cov.: 31 AF XY: 0.00256 AC XY: 1822 AN XY: 710568

Gnomad4 AFR exome AF: 0.000317

Gnomad4 AMR exome AF: 0.000164

Gnomad4 ASJ exome AF: 0.000572

Gnomad4 EAS exome AF: 0.0828

Gnomad4 SAS exome AF: 0.00167

Gnomad4 FIN exome AF: 0.00157

Gnomad4 NFE exome AF: 0.0000563

Gnomad4 OTH exome AF: 0.00339

GnomAD4 genome AF: 0.00380 AC: 578 AN: 152172 Hom.: 30 Cov.: 32 AF XY: 0.00450 AC XY: 335 AN XY: 74396

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0907

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000801 Hom.: 0

Bravo AF: 0.00478

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 21, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 07, 2012

8567-13C>T in Intron 37 of GPR98: This variant is not expected to have clinical significance because it has been identified in 5.0% (6/120) of chromosomes from a population in the dbSNP database (http://www.ncbi.nlm.nih.gov/projects/SNP; rs 75881968). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.8
Dann	Benign	0.29

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: rs75881968; hg19: chr5-90002035;