rs80069610

Variant names:

• chr5-90651617-A-G
• rs80069610
• NM_032119.4:c.3303A>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.3303A>G​(p.Val1101Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,579,550 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (20 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.269
• Publications: 3 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: ClinGen, Orphanet
• Usher syndrome type 2C

  Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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 5-90651617-A-G is Benign according to our data. Variant chr5-90651617-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.269 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00163 (249/152330) while in subpopulation EAS AF = 0.0226 (117/5182). AF 95% confidence interval is 0.0193. There are 3 homozygotes in GnomAd4. There are 150 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD 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.3303A>G	p.Val1101Val	synonymous	Exon 18 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.3402A>G		non_coding_transcript_exon	Exon 18 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.3303A>G	p.Val1101Val	synonymous	Exon 18 of 90	ENSP00000384582.2
	ADGRV1	ENST00000640403.1	TSL:5	c.606A>G	p.Val202Val	synonymous	Exon 8 of 29	ENSP00000492531.1
	ADGRV1	ENST00000504142.2	TSL:5	n.2069A>G		non_coding_transcript_exon	Exon 12 of 14

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 249 AN: 152212 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00734

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00262 AC: 642 AN: 245450 AF XY: 0.00247

Gnomad AFR exome AF: 0.0000657

Gnomad AMR exome AF: 0.00115

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0191

Gnomad FIN exome AF: 0.00662

Gnomad NFE exome AF: 0.000861

Gnomad OTH exome AF: 0.00134

GnomAD4 exome AF: 0.00113 AC: 1610 AN: 1427220 Hom.: 20 Cov.: 26 AF XY: 0.00107 AC XY: 764 AN XY: 711646

African (AFR) AF: 0.0000609 AC: 2 AN: 32816

American (AMR) AF: 0.00102 AC: 45 AN: 44226

Ashkenazi Jewish (ASJ) AF: 0.0000388 AC: 1 AN: 25784

East Asian (EAS) AF: 0.0194 AC: 762 AN: 39354

South Asian (SAS) AF: 0.000533 AC: 45 AN: 84370

European-Finnish (FIN) AF: 0.00666 AC: 354 AN: 53178

Middle Eastern (MID) AF: 0.000530 AC: 3 AN: 5664

European-Non Finnish (NFE) AF: 0.000291 AC: 315 AN: 1082604

Other (OTH) AF: 0.00140 AC: 83 AN: 59224

GnomAD4 genome AF: 0.00163 AC: 249 AN: 152330 Hom.: 3 Cov.: 32 AF XY: 0.00201 AC XY: 150 AN XY: 74484

African (AFR) AF: 0.0000481 AC: 2 AN: 41576

American (AMR) AF: 0.000849 AC: 13 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0226 AC: 117 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4826

European-Finnish (FIN) AF: 0.00734 AC: 78 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000409 Hom.: 0

Bravo AF: 0.00130

Asia WGS AF: 0.00810 AC: 29 AN: 3472

ClinVar

ClinVar submissions as Germline

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	-0.55
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		-0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs80069610; hg19: chr5-89947434; COSMIC: COSV67997835;