5-90848679-C-A

Variant names:

• chr5-90848679-C-A
• rs747622607
• NM_032119.4:c.17062C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_032119.4(ADGRV1):​c.17062C>A​(p.Arg5688Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• 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: ClinGen, Orphanet
• Usher syndrome type 2C

  Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.14).
• BP7: Synonymous conserved (PhyloP=2.23 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.17062C>A	p.Arg5688Arg	synonymous_variant	Exon 79 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.17062C>A	p.Arg5688Arg	synonymous_variant	Exon 79 of 90	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408066 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 697378

African (AFR) AF: 0.00 AC: 0 AN: 31154

American (AMR) AF: 0.00 AC: 0 AN: 36110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25036

East Asian (EAS) AF: 0.00 AC: 0 AN: 36670

South Asian (SAS) AF: 0.00 AC: 0 AN: 73044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089774

Other (OTH) AF: 0.00 AC: 0 AN: 58176

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs747622607; hg19: chr5-90144496;