chr5-90693962-G-A

Variant names:

• chr5-90693962-G-A
• rs16876822
• NM_032119.4:c.7206G>A

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.7206G>A​(p.Glu2402Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,606,424 control chromosomes in the GnomAD database, including 97,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8087 hom., cov: 32)
  • Exomes 𝑓: 0.35 (89238 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.703
• Publications: 21 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 (BayesDel_noAF=-0.56).
• BP6: Variant 5-90693962-G-A is Benign according to our data. Variant chr5-90693962-G-A is described in ClinVar as Benign. ClinVar VariationId is 46365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.703 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.464 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.7206G>A	p.Glu2402Glu	synonymous	Exon 33 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.7222G>A		non_coding_transcript_exon	Exon 33 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.7206G>A	p.Glu2402Glu	synonymous	Exon 33 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.4497G>A	p.Glu1499Glu	synonymous	Exon 23 of 29	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000639473.1	TSL:5	n.2665G>A		non_coding_transcript_exon	Exon 13 of 23

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47946 AN: 151910 Hom.: 8074 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.350

GnomAD2 exomes AF: 0.360 AC: 88481 AN: 246020 AF XY: 0.352

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.582

Gnomad ASJ exome AF: 0.268

Gnomad EAS exome AF: 0.368

Gnomad FIN exome AF: 0.336

Gnomad NFE exome AF: 0.334

Gnomad OTH exome AF: 0.364

GnomAD4 exome AF: 0.346 AC: 502513 AN: 1454396 Hom.: 89238 Cov.: 37 AF XY: 0.343 AC XY: 247735 AN XY: 722126

African (AFR) AF: 0.205 AC: 6833 AN: 33352

American (AMR) AF: 0.569 AC: 25215 AN: 44326

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7073 AN: 25974

East Asian (EAS) AF: 0.433 AC: 17095 AN: 39482

South Asian (SAS) AF: 0.328 AC: 28181 AN: 85932

European-Finnish (FIN) AF: 0.341 AC: 18130 AN: 53226

Middle Eastern (MID) AF: 0.274 AC: 1572 AN: 5734

European-Non Finnish (NFE) AF: 0.342 AC: 378218 AN: 1106374

Other (OTH) AF: 0.337 AC: 20196 AN: 59996

GnomAD4 genome AF: 0.316 AC: 47965 AN: 152028 Hom.: 8087 Cov.: 32 AF XY: 0.319 AC XY: 23681 AN XY: 74308

African (AFR) AF: 0.215 AC: 8931 AN: 41470

American (AMR) AF: 0.474 AC: 7233 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3466

East Asian (EAS) AF: 0.386 AC: 1990 AN: 5158

South Asian (SAS) AF: 0.321 AC: 1547 AN: 4818

European-Finnish (FIN) AF: 0.334 AC: 3528 AN: 10562

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22647 AN: 67968

Other (OTH) AF: 0.345 AC: 729 AN: 2110

Alfa AF: 0.328 Hom.: 26261

Bravo AF: 0.328

Asia WGS AF: 0.343 AC: 1194 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C (1)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.8
DANN	Benign	0.50
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs16876822; hg19: chr5-89989779; COSMIC: COSV67980898; COSMIC: COSV67980898;