rs10040165

Variant names:

• chr5-90692595-G-A
• rs10040165
• NM_032119.4:c.6952-10G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_032119.4(ADGRV1):​c.6952-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,584,942 control chromosomes in the GnomAD database, including 94,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8057 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86610 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Scores: Splicing: ADA: 0.0001884
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.469
• Publications: 15 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 5-90692595-G-A is Benign according to our data. Variant chr5-90692595-G-A is described in ClinVar as Benign. ClinVar VariationId is 46358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.463 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.6952-10G>A		intron	N/A	NP_115495.3
	ADGRV1	NR_003149.2		n.6968-10G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.6952-10G>A		intron	N/A	ENSP00000384582.2
	ADGRV1	ENST00000640403.1	TSL:5	c.4243-10G>A		intron	N/A	ENSP00000492531.1
	ADGRV1	ENST00000639431.1	TSL:5	n.265+16386G>A		intron	N/A	ENSP00000491057.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47886 AN: 151806 Hom.: 8044 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.348

GnomAD2 exomes AF: 0.348 AC: 78709 AN: 226266 AF XY: 0.341

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.565

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.361

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.327

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.342 AC: 490657 AN: 1433018 Hom.: 86610 Cov.: 29 AF XY: 0.340 AC XY: 242185 AN XY: 711990

African (AFR) AF: 0.202 AC: 6586 AN: 32682

American (AMR) AF: 0.553 AC: 21803 AN: 39432

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 6877 AN: 25576

East Asian (EAS) AF: 0.432 AC: 16866 AN: 39054

South Asian (SAS) AF: 0.322 AC: 26224 AN: 81396

European-Finnish (FIN) AF: 0.340 AC: 17978 AN: 52908

Middle Eastern (MID) AF: 0.274 AC: 1562 AN: 5710

European-Non Finnish (NFE) AF: 0.340 AC: 372927 AN: 1096872

Other (OTH) AF: 0.334 AC: 19834 AN: 59388

GnomAD4 genome AF: 0.315 AC: 47905 AN: 151924 Hom.: 8057 Cov.: 32 AF XY: 0.319 AC XY: 23647 AN XY: 74230

African (AFR) AF: 0.215 AC: 8926 AN: 41454

American (AMR) AF: 0.472 AC: 7205 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3466

East Asian (EAS) AF: 0.387 AC: 1995 AN: 5156

South Asian (SAS) AF: 0.322 AC: 1547 AN: 4810

European-Finnish (FIN) AF: 0.334 AC: 3518 AN: 10524

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

European-Non Finnish (NFE) AF: 0.333 AC: 22629 AN: 67938

Other (OTH) AF: 0.344 AC: 725 AN: 2110

Alfa AF: 0.335 Hom.: 12058

Bravo AF: 0.327

Asia WGS AF: 0.343 AC: 1193 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	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	-0.42
CADD	Benign	14
DANN	Benign	0.63
PhyloP100		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.030		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: rs10040165; hg19: chr5-89988412; COSMIC: COSV67980893; COSMIC: COSV67980893;