rs145294917

chr5-90745617-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_032119.4(ADGRV1):c.10796G>C(p.Gly3599Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000643 in 1,611,954 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (7 hom.)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 5.22

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 (MetaRNN=0.009105235).
• BP6: Variant 5-90745617-G-C is Benign according to our data. Variant chr5-90745617-G-C is described in ClinVar as [Benign]. Clinvar id is 163596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90745617-G-C is described in Lovd as [Benign]. Variant chr5-90745617-G-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00362 (551/152210) while in subpopulation AFR AF= 0.0121 (504/41538). AF 95% confidence interval is 0.0113. There are 1 homozygotes in gnomad4. There are 252 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4	c.10796G>C	p.Gly3599Ala	missense_variant	52/90	ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.10796G>C	p.Gly3599Ala	missense_variant	52/90	1	NM_032119.4	P1

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 551 AN: 152092 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000898 AC: 223 AN: 248350 Hom.: 1 AF XY: 0.000601 AC XY: 81 AN XY: 134720

Gnomad AFR exome AF: 0.0131

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.000499

GnomAD4 exome AF: 0.000333 AC: 486 AN: 1459744 Hom.: 7 Cov.: 29 AF XY: 0.000267 AC XY: 194 AN XY: 726206

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000810

Gnomad4 OTH exome AF: 0.000863

GnomAD4 genome AF: 0.00362 AC: 551 AN: 152210 Hom.: 1 Cov.: 32 AF XY: 0.00339 AC XY: 252 AN XY: 74428

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000572 Hom.: 0

Bravo AF: 0.00407

ESP6500AA AF: 0.0131 AC: 48

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00109 AC: 132

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 04, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Gly3599Ala in Exon 52 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 1.4% (40/2958) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs145294917). -

ADGRV1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 24, 2019

This variant is classified as 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
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.99	D
MetaRNN	Benign	0.0091	T;T
MetaSVM	Benign	-0.34	T
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.46	T
Polyphen		1.0	D;D
Vest4		0.64
MVP		0.66
MPC		0.34
ClinPred		0.058	T
GERP RS		4.1
Varity_R		0.42
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs145294917; hg19: chr5-90041434;