rs73181640

Variant names:

• chr5-90643052-T-A
• rs73181640
• NM_032119.4:c.2553+11T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032119.4(ADGRV1):​c.2553+11T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00365 in 1,602,940 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (59 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.671
• Publications: 2 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=-0.8).
• BP6: Variant 5-90643052-T-A is Benign according to our data. Variant chr5-90643052-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00605 (922/152292) while in subpopulation SAS AF = 0.0187 (90/4824). AF 95% confidence interval is 0.0155. There are 4 homozygotes in GnomAd4. There are 472 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 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.2553+11T>A		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.2652+11T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.2553+11T>A		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.-145+11T>A		intron	N/A	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000504142.2	TSL:5	n.1319+11T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00606 AC: 922 AN: 152174 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00592 AC: 1465 AN: 247328 AF XY: 0.00675

Gnomad AFR exome AF: 0.0147

Gnomad AMR exome AF: 0.00324

Gnomad ASJ exome AF: 0.0136

Gnomad EAS exome AF: 0.0000558

Gnomad FIN exome AF: 0.00154

Gnomad NFE exome AF: 0.00220

Gnomad OTH exome AF: 0.00687

GnomAD4 exome AF: 0.00339 AC: 4921 AN: 1450648 Hom.: 59 Cov.: 28 AF XY: 0.00392 AC XY: 2835 AN XY: 722354

African (AFR) AF: 0.0133 AC: 442 AN: 33188

American (AMR) AF: 0.00299 AC: 133 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 352 AN: 25958

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39628

South Asian (SAS) AF: 0.0202 AC: 1729 AN: 85748

European-Finnish (FIN) AF: 0.00176 AC: 94 AN: 53340

Middle Eastern (MID) AF: 0.0324 AC: 186 AN: 5748

European-Non Finnish (NFE) AF: 0.00151 AC: 1669 AN: 1102542

Other (OTH) AF: 0.00525 AC: 315 AN: 59956

GnomAD4 genome AF: 0.00605 AC: 922 AN: 152292 Hom.: 4 Cov.: 32 AF XY: 0.00634 AC XY: 472 AN XY: 74470

African (AFR) AF: 0.0138 AC: 575 AN: 41552

American (AMR) AF: 0.00386 AC: 59 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0187 AC: 90 AN: 4824

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00181 AC: 123 AN: 68020

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00626 Hom.: 2

Bravo AF: 0.00588

Asia WGS AF: 0.00953 AC: 34 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	-0.80
CADD	Benign	7.5
DANN	Benign	0.76
PhyloP100		0.67
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: rs73181640; hg19: chr5-89938869;