chr5-90706403-CTTTT-C

Variant names:

• chr5-90706403-CTTTT-C
• rs60522638
• NM_032119.4:c.8730+18_8730+21delTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032119.4(ADGRV1):​c.8730+18_8730+21delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000814 in 1,228,446 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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+18_8730+21delTTTT		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.8746+18_8746+21delTTTT		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+10_8730+13delTTTT		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.1427+10_1427+13delTTTT		intron	N/A
	ADGRV1	ENST00000640403.1	TSL:5	c.6021+10_6021+13delTTTT		intron	N/A	ENSP00000492531.1	A0A1W2PRC7

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 8.14e-7 AC: 1 AN: 1228446 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 607546

African (AFR) AF: 0.00 AC: 0 AN: 25456

American (AMR) AF: 0.00 AC: 0 AN: 23768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21222

East Asian (EAS) AF: 0.00 AC: 0 AN: 33398

South Asian (SAS) AF: 0.00 AC: 0 AN: 64108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4936

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 958556

Other (OTH) AF: 0.00 AC: 0 AN: 51106

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

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;