5-90706403-CTTTT-CTTT

Variant names:

• chr5-90706403-CT-C
• rs60522638
• NM_032119.4:c.8730+21delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_032119.4(ADGRV1):​c.8730+21delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 1,318,768 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (5 hom., cov: 0)
  • Exomes 𝑓: 0.029 (2 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.0450
• 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: 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 -10 ACMG points.

• BP6: Variant 5-90706403-CT-C is Benign according to our data. Variant chr5-90706403-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1164935.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00489 (716/146368) while in subpopulation AFR AF = 0.0148 (593/40002). AF 95% confidence interval is 0.0138. There are 5 homozygotes in GnomAd4. There are 360 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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.8730+21delT		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.8746+21delT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.8730+10delT		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.1427+10delT		intron	N/A
	ADGRV1	ENST00000640403.1	TSL:5	c.6021+10delT		intron	N/A	ENSP00000492531.1	A0A1W2PRC7

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 714 AN: 146294 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.0408

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00153

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00201

GnomAD2 exomes AF: 0.0368 AC: 4112 AN: 111634 AF XY: 0.0390

Gnomad AFR exome AF: 0.0344

Gnomad AMR exome AF: 0.0288

Gnomad ASJ exome AF: 0.0513

Gnomad EAS exome AF: 0.0167

Gnomad FIN exome AF: 0.0240

Gnomad NFE exome AF: 0.0437

Gnomad OTH exome AF: 0.0396

GnomAD4 exome AF: 0.0287 AC: 33668 AN: 1172400 Hom.: 2 Cov.: 25 AF XY: 0.0290 AC XY: 16827 AN XY: 579668

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0256 AC: 636 AN: 24820

American (AMR) AF: 0.0226 AC: 521 AN: 23042

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 658 AN: 20258

East Asian (EAS) AF: 0.0126 AC: 409 AN: 32434

South Asian (SAS) AF: 0.0304 AC: 1882 AN: 61886

European-Finnish (FIN) AF: 0.0280 AC: 1213 AN: 43312

Middle Eastern (MID) AF: 0.0204 AC: 98 AN: 4800

European-Non Finnish (NFE) AF: 0.0295 AC: 26924 AN: 912804

Other (OTH) AF: 0.0271 AC: 1327 AN: 49044

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00489 AC: 716 AN: 146368 Hom.: 5 Cov.: 0 AF XY: 0.00506 AC XY: 360 AN XY: 71172

African (AFR) AF: 0.0148 AC: 593 AN: 40002

American (AMR) AF: 0.00137 AC: 20 AN: 14600

Ashkenazi Jewish (ASJ) AF: 0.00117 AC: 4 AN: 3406

East Asian (EAS) AF: 0.00 AC: 0 AN: 4944

South Asian (SAS) AF: 0.000217 AC: 1 AN: 4612

European-Finnish (FIN) AF: 0.00153 AC: 14 AN: 9166

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

European-Non Finnish (NFE) AF: 0.000647 AC: 43 AN: 66430

Other (OTH) AF: 0.00199 AC: 4 AN: 2010

Alfa AF: 0.00 Hom.: 717

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.045
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: rs60522638; hg19: chr5-90002220; COSMIC: COSV67993611;