5-90740272-A-G

Variant names:

• chr5-90740272-A-G
• rs2222244
• NM_032119.4:c.10550-4774A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032119.4(ADGRV1):​c.10550-4774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 151,868 control chromosomes in the GnomAD database, including 39,746 homozygotes. 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: 𝑓 0.72 (39746 hom., cov: 29)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.10550-4774A>G		intron_variant	Intron 50 of 89	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.10550-4774A>G		intron_variant	Intron 50 of 89	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109066 AN: 151748 Hom.: 39677 Cov.: 29

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.719

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.719 AC: 109203 AN: 151868 Hom.: 39746 Cov.: 29 AF XY: 0.725 AC XY: 53865 AN XY: 74246

African (AFR) AF: 0.815 AC: 33780 AN: 41436

American (AMR) AF: 0.770 AC: 11760 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2304 AN: 3464

East Asian (EAS) AF: 0.796 AC: 4094 AN: 5144

South Asian (SAS) AF: 0.704 AC: 3378 AN: 4798

European-Finnish (FIN) AF: 0.726 AC: 7664 AN: 10562

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.647 AC: 43908 AN: 67896

Other (OTH) AF: 0.723 AC: 1520 AN: 2102

Alfa AF: 0.674 Hom.: 154660

Bravo AF: 0.729

Asia WGS AF: 0.791 AC: 2749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.52
PhyloP100		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2222244; hg19: chr5-90036089;