rs61749567

chr5-90629517-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032119.4(ADGRV1):c.1817A>C(p.Asn606Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00155 in 1,611,358 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. N606N) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0087 (21 hom., cov: 31)
  • Exomes 𝑓: 0.00081 (15 hom.)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 6.86

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 (MetaRNN=0.009265631).
• BP6: Variant 5-90629517-A-C is Benign according to our data. Variant chr5-90629517-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 46296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90629517-A-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00868 (1321/152238) while in subpopulation AFR AF= 0.0307 (1274/41542). AF 95% confidence interval is 0.0293. There are 21 homozygotes in gnomad4. There are 597 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4	c.1817A>C	p.Asn606Thr	missense_variant	9/90	ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.1817A>C	p.Asn606Thr	missense_variant	9/90	1	NM_032119.4	P1
ADGRV1	ENST00000504142.2	n.583A>C		non_coding_transcript_exon_variant	3/14	5
ADGRV1	ENST00000640109.1	n.1913A>C		non_coding_transcript_exon_variant	9/9	5

Frequencies

GnomAD3 genomes AF: 0.00866 AC: 1317 AN: 152120 Hom.: 21 Cov.: 31

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00218 AC: 537 AN: 246804 Hom.: 12 AF XY: 0.00163 AC XY: 219 AN XY: 134202

Gnomad AFR exome AF: 0.0318

Gnomad AMR exome AF: 0.00105

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000626

Gnomad OTH exome AF: 0.000671

GnomAD4 exome AF: 0.000810 AC: 1182 AN: 1459120 Hom.: 15 Cov.: 31 AF XY: 0.000708 AC XY: 514 AN XY: 725936

Gnomad4 AFR exome AF: 0.0293

Gnomad4 AMR exome AF: 0.00124

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome AF: 0.00868 AC: 1321 AN: 152238 Hom.: 21 Cov.: 31 AF XY: 0.00802 AC XY: 597 AN XY: 74416

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00162 Hom.: 5

Bravo AF: 0.00970

ESP6500AA AF: 0.0328 AC: 121

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00277 AC: 335

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely 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	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 04, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 23, 2017	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	Apr 30, 2012	Asn606Thr in Exon 09 of GPR98: This variant is not expected to have clinical sig nificance because it has been identified in 3.2% (96/2992) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs61749567). -

Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.47
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.20	T;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
MetaRNN	Benign	0.0093	T;T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.67	T
Polyphen		1.0	D;D
Vest4		0.78
MVP		0.78
MPC		0.23
ClinPred		0.026	T
GERP RS		5.5
Varity_R		0.24
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61749567; hg19: chr5-89925334;