5-90725106-T-C

Variant names:

• chr5-90725106-T-C
• rs16869042
• NM_032119.4:c.9927T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032119.4(ADGRV1):​c.9927T>C​(p.Pro3309Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,938 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. Synonymous variant affecting the same amino acid position (i.e. P3309P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• 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

LOC105379077 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.012).
• BP7: Synonymous conserved (PhyloP=-0.012 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.9927T>C	p.Pro3309Pro	synonymous_variant	Exon 47 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.9927T>C	p.Pro3309Pro	synonymous_variant	Exon 47 of 90	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1386938 Hom.: 0 Cov.: 27 AF XY: 0.00000145 AC XY: 1 AN XY: 691760

African (AFR) AF: 0.00 AC: 0 AN: 30362

American (AMR) AF: 0.00 AC: 0 AN: 31286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24444

East Asian (EAS) AF: 0.00 AC: 0 AN: 38958

South Asian (SAS) AF: 0.00 AC: 0 AN: 77394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5534

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068224

Other (OTH) AF: 0.0000173 AC: 1 AN: 57704

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.1
DANN	Benign	0.66
PhyloP100		-0.012

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: rs16869042; hg19: chr5-90020923;