5-90914007-C-T

Variant names:

• chr5-90914007-C-T
• rs10074525
• NM_032119.4:c.17856+50150C>T

Variant summary

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

The NM_032119.4(ADGRV1):​c.17856+50150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,078 control chromosomes in the GnomAD database, including 42,268 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 0.74 (42268 hom., cov: 31)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

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.17856+50150C>T		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.17872+50150C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.17856+50150C>T		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000638510.1	TSL:1	n.5123+50150C>T		intron	N/A
	ADGRV1	ENST00000425867.3	TSL:5	c.6810+50150C>T		intron	N/A	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112772 AN: 151960 Hom.: 42231 Cov.: 31

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.742 AC: 112871 AN: 152078 Hom.: 42268 Cov.: 31 AF XY: 0.749 AC XY: 55655 AN XY: 74330

African (AFR) AF: 0.759 AC: 31518 AN: 41510

American (AMR) AF: 0.836 AC: 12770 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2278 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5172 AN: 5184

South Asian (SAS) AF: 0.851 AC: 4109 AN: 4826

European-Finnish (FIN) AF: 0.692 AC: 7304 AN: 10556

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47218 AN: 67948

Other (OTH) AF: 0.770 AC: 1627 AN: 2112

Alfa AF: 0.717 Hom.: 130432

Bravo AF: 0.751

Asia WGS AF: 0.922 AC: 3203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.68
DANN	Benign	0.49
PhyloP100		-0.27
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: rs10074525; hg19: chr5-90209824;