rs2366773

Variant names:

• chr5-90642770-C-T
• rs2366773
• NM_032119.4:c.2367+8C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-90642770-C-T
• chr5-90642770-C-A
• chr5-90642770-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032119.4(ADGRV1):​c.2367+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 1,607,338 control chromosomes in the GnomAD database, including 393,400 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (45027 hom., cov: 32)
  • Exomes 𝑓: 0.69 (348373 hom.)
• Consequence: ADGRV1 NM_032119.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001225
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.448
• 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: 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-90642770-C-T is Benign according to our data. Variant chr5-90642770-C-T is described in ClinVar as Benign. ClinVar VariationId is 46305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 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.2367+8C>T		splice_region intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.2466+8C>T		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.2367+8C>T		splice_region intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.-331+8C>T		splice_region intron	N/A	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000504142.2	TSL:5	n.1133+8C>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115669 AN: 151958 Hom.: 44952 Cov.: 32

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.754

GnomAD2 exomes AF: 0.733 AC: 178748 AN: 243920 AF XY: 0.725

Gnomad AFR exome AF: 0.925

Gnomad AMR exome AF: 0.835

Gnomad ASJ exome AF: 0.688

Gnomad EAS exome AF: 0.807

Gnomad FIN exome AF: 0.690

Gnomad NFE exome AF: 0.672

Gnomad OTH exome AF: 0.729

GnomAD4 exome AF: 0.689 AC: 1003013 AN: 1455262 Hom.: 348373 Cov.: 41 AF XY: 0.689 AC XY: 498711 AN XY: 723828

African (AFR) AF: 0.926 AC: 30458 AN: 32896

American (AMR) AF: 0.830 AC: 36017 AN: 43394

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 17867 AN: 25798

East Asian (EAS) AF: 0.821 AC: 32551 AN: 39658

South Asian (SAS) AF: 0.747 AC: 63432 AN: 84860

European-Finnish (FIN) AF: 0.689 AC: 36726 AN: 53318

Middle Eastern (MID) AF: 0.709 AC: 4058 AN: 5720

European-Non Finnish (NFE) AF: 0.666 AC: 739026 AN: 1109572

Other (OTH) AF: 0.714 AC: 42878 AN: 60046

GnomAD4 genome AF: 0.761 AC: 115801 AN: 152076 Hom.: 45027 Cov.: 32 AF XY: 0.763 AC XY: 56725 AN XY: 74316

African (AFR) AF: 0.920 AC: 38241 AN: 41548

American (AMR) AF: 0.789 AC: 12047 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2416 AN: 3470

East Asian (EAS) AF: 0.819 AC: 4233 AN: 5170

South Asian (SAS) AF: 0.751 AC: 3626 AN: 4830

European-Finnish (FIN) AF: 0.684 AC: 7219 AN: 10558

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45548 AN: 67926

Other (OTH) AF: 0.758 AC: 1596 AN: 2106

Alfa AF: 0.692 Hom.: 30944

Bravo AF: 0.778

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.45
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0
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: rs2366773; hg19: chr5-89938587;