rs146120983

chr5-90855881-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_032119.4(ADGRV1):c.17735C>G(p.Ser5912Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000366 in 1,612,812 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (2 hom.)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 7.65

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009422094).
• BP6: Variant 5-90855881-C-G is Benign according to our data. Variant chr5-90855881-C-G is described in ClinVar as [Benign]. Clinvar id is 198950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4	c.17735C>G	p.Ser5912Cys	missense_variant	82/90	ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.17735C>G	p.Ser5912Cys	missense_variant	82/90	1	NM_032119.4	P1

Frequencies

GnomAD3 genomes AF: 0.00180 AC: 274 AN: 152154 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00611

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

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: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000510 AC: 127 AN: 248796 Hom.: 1 AF XY: 0.000385 AC XY: 52 AN XY: 134970

Gnomad AFR exome AF: 0.00685

Gnomad AMR exome AF: 0.000494

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000213 AC: 311 AN: 1460540 Hom.: 2 Cov.: 29 AF XY: 0.000187 AC XY: 136 AN XY: 726602

Gnomad4 AFR exome AF: 0.00720

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.000680

GnomAD4 genome AF: 0.00184 AC: 280 AN: 152272 Hom.: 1 Cov.: 32 AF XY: 0.00183 AC XY: 136 AN XY: 74456

Gnomad4 AFR AF: 0.00623

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000491 Hom.: 0

Bravo AF: 0.00216

ESP6500AA AF: 0.00843 AC: 32

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000571 AC: 69

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 18, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Ser5912Cys in Exon 82 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 0.7% (23/3110) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs146120983). -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 28, 2020	This variant is associated with the following publications: (PMID: 26969326) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.15
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.0094	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
Polyphen		0.99	D;D;.
Vest4		0.73
MVP		0.75
MPC		0.31
ClinPred		0.032	T
GERP RS		5.5
Varity_R		0.22
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs146120983; hg19: chr5-90151698;