rs950692

Variant names:

• chr5-90647616-A-G
• rs950692
• NM_032119.4:c.3141A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):​c.3141A>G​(p.Ala1047Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,613,534 control chromosomes in the GnomAD database, including 17,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2067 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15096 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.00
• Publications: 20 publications found

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]

ADGRV1 Gene-Disease associations (from GenCC):

• Usher syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Usher syndrome type 2C

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• febrile seizures, familial, 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.011).
• BP6: Variant 5-90647616-A-G is Benign according to our data. Variant chr5-90647616-A-G is described in ClinVar as Benign. ClinVar VariationId is 46310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.3141A>G	p.Ala1047Ala	synonymous	Exon 17 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.3240A>G		non_coding_transcript_exon	Exon 17 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.3141A>G	p.Ala1047Ala	synonymous	Exon 17 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.444A>G	p.Ala148Ala	synonymous	Exon 7 of 29	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000504142.2	TSL:5	n.1907A>G		non_coding_transcript_exon	Exon 11 of 14

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23922 AN: 152046 Hom.: 2056 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.165

GnomAD2 exomes AF: 0.165 AC: 41121 AN: 248978 AF XY: 0.165

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.363

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.136 AC: 198756 AN: 1461370 Hom.: 15096 Cov.: 33 AF XY: 0.138 AC XY: 100544 AN XY: 726970

African (AFR) AF: 0.190 AC: 6367 AN: 33468

American (AMR) AF: 0.138 AC: 6182 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5340 AN: 26126

East Asian (EAS) AF: 0.338 AC: 13393 AN: 39678

South Asian (SAS) AF: 0.200 AC: 17229 AN: 86238

European-Finnish (FIN) AF: 0.162 AC: 8673 AN: 53400

Middle Eastern (MID) AF: 0.169 AC: 977 AN: 5766

European-Non Finnish (NFE) AF: 0.118 AC: 131110 AN: 1111612

Other (OTH) AF: 0.157 AC: 9485 AN: 60358

GnomAD4 genome AF: 0.158 AC: 23966 AN: 152164 Hom.: 2067 Cov.: 32 AF XY: 0.162 AC XY: 12056 AN XY: 74386

African (AFR) AF: 0.184 AC: 7624 AN: 41512

American (AMR) AF: 0.144 AC: 2193 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1889 AN: 5168

South Asian (SAS) AF: 0.205 AC: 984 AN: 4810

European-Finnish (FIN) AF: 0.160 AC: 1700 AN: 10598

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8371 AN: 68008

Other (OTH) AF: 0.173 AC: 365 AN: 2114

Alfa AF: 0.138 Hom.: 6636

Bravo AF: 0.158

Asia WGS AF: 0.300 AC: 1040 AN: 3476

EpiCase AF: 0.128

EpiControl AF: 0.130

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Usher syndrome type 2C (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.19
DANN	Benign	0.48
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs950692; hg19: chr5-89943433; COSMIC: COSV67978723;