rs61740119

Variant names:

• chr5-90653834-A-G
• rs61740119
• NM_032119.4:c.4260A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032119.4(ADGRV1):​c.4260A>G​(p.Glu1420Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,612,894 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (46 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.780
• Publications: 5 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=0.014).
• BP6: Variant 5-90653834-A-G is Benign according to our data. Variant chr5-90653834-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.78 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00549 (836/152328) while in subpopulation SAS AF = 0.0126 (61/4830). AF 95% confidence interval is 0.0101. There are 3 homozygotes in GnomAd4. There are 408 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

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.4260A>G	p.Glu1420Glu	synonymous	Exon 20 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.4359A>G		non_coding_transcript_exon	Exon 20 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.4260A>G	p.Glu1420Glu	synonymous	Exon 20 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.1551A>G	p.Glu517Glu	synonymous	Exon 10 of 29	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000504142.2	TSL:5	n.3026A>G		non_coding_transcript_exon	Exon 14 of 14

Frequencies

GnomAD3 genomes AF: 0.00552 AC: 840 AN: 152210 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00982

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00332

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00562 AC: 1387 AN: 246698 AF XY: 0.00594

Gnomad AFR exome AF: 0.00992

Gnomad AMR exome AF: 0.00728

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00205

Gnomad NFE exome AF: 0.00306

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.00407 AC: 5943 AN: 1460566 Hom.: 46 Cov.: 32 AF XY: 0.00432 AC XY: 3138 AN XY: 726394

African (AFR) AF: 0.00938 AC: 314 AN: 33480

American (AMR) AF: 0.00694 AC: 309 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 307 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0133 AC: 1145 AN: 85894

European-Finnish (FIN) AF: 0.00253 AC: 135 AN: 53354

Middle Eastern (MID) AF: 0.0298 AC: 172 AN: 5768

European-Non Finnish (NFE) AF: 0.00288 AC: 3206 AN: 1111386

Other (OTH) AF: 0.00588 AC: 355 AN: 60346

GnomAD4 genome AF: 0.00549 AC: 836 AN: 152328 Hom.: 3 Cov.: 32 AF XY: 0.00548 AC XY: 408 AN XY: 74482

African (AFR) AF: 0.00977 AC: 406 AN: 41572

American (AMR) AF: 0.00438 AC: 67 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0126 AC: 61 AN: 4830

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00332 AC: 226 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00472 Hom.: 1

Bravo AF: 0.00564

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	4	not specified (4)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.4
DANN	Benign	0.56
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism

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: rs61740119; hg19: chr5-89949651;