5-90706403-CTTTT-CTTTTTT

Variant names:

• chr5-90706403-C-CTT
• rs60522638
• NM_032119.4:c.8730+20_8730+21dupTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_032119.4(ADGRV1):​c.8730+20_8730+21dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00851 in 1,355,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0095 (0 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 5-90706403-C-CTT is Benign according to our data. Variant chr5-90706403-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 1165478.Status of the report is criteria_provided_single_submitter, 1 stars.

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+20_8730+21dupTT		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.8746+20_8746+21dupTT		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+9_8730+10insTT		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.1427+9_1427+10insTT		intron	N/A
	ADGRV1	ENST00000640403.1	TSL:5	c.6021+9_6021+10insTT		intron	N/A	ENSP00000492531.1	A0A1W2PRC7

Frequencies

GnomAD3 genomes AF: 0.000225 AC: 33 AN: 146426 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000351

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000343

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000605

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000109

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0103 AC: 1148 AN: 111634 AF XY: 0.0104

Gnomad AFR exome AF: 0.0134

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.0116

Gnomad EAS exome AF: 0.0126

Gnomad FIN exome AF: 0.00459

Gnomad NFE exome AF: 0.00980

Gnomad OTH exome AF: 0.00799

GnomAD4 exome AF: 0.00951 AC: 11493 AN: 1208528 Hom.: 0 Cov.: 25 AF XY: 0.00932 AC XY: 5571 AN XY: 597936

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

African (AFR) AF: 0.0155 AC: 385 AN: 24878

American (AMR) AF: 0.0107 AC: 251 AN: 23466

Ashkenazi Jewish (ASJ) AF: 0.00994 AC: 208 AN: 20920

East Asian (EAS) AF: 0.00886 AC: 290 AN: 32722

South Asian (SAS) AF: 0.0111 AC: 704 AN: 63154

European-Finnish (FIN) AF: 0.00538 AC: 243 AN: 45198

Middle Eastern (MID) AF: 0.00863 AC: 42 AN: 4868

European-Non Finnish (NFE) AF: 0.00940 AC: 8864 AN: 943038

Other (OTH) AF: 0.0101 AC: 506 AN: 50284

⚠️ 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: 0.000225 AC: 33 AN: 146498 Hom.: 0 Cov.: 0 AF XY: 0.000267 AC XY: 19 AN XY: 71250

African (AFR) AF: 0.000350 AC: 14 AN: 40030

American (AMR) AF: 0.000342 AC: 5 AN: 14608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3406

East Asian (EAS) AF: 0.000607 AC: 3 AN: 4946

South Asian (SAS) AF: 0.00 AC: 0 AN: 4612

European-Finnish (FIN) AF: 0.000109 AC: 1 AN: 9200

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

European-Non Finnish (NFE) AF: 0.000150 AC: 10 AN: 66488

Other (OTH) AF: 0.00 AC: 0 AN: 2010

Alfa AF: 0.00 Hom.: 717

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.045
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs60522638; hg19: chr5-90002220;