rs12522395

Variant names:

• chr5-90914701-G-C
• rs12522395
• NM_032119.4:c.17857-50714G>C

Variant summary

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

The NM_032119.4(ADGRV1):​c.17857-50714G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,942 control chromosomes in the GnomAD database, including 6,451 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 0.28 (6451 hom., cov: 32)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 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.17857-50714G>C		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.17873-50714G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.17857-50714G>C		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000638510.1	TSL:1	n.5124-50714G>C		intron	N/A
	ADGRV1	ENST00000425867.3	TSL:5	c.6811-50714G>C		intron	N/A	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42299 AN: 151824 Hom.: 6448 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.279 AC: 42328 AN: 151942 Hom.: 6451 Cov.: 32 AF XY: 0.277 AC XY: 20572 AN XY: 74262

African (AFR) AF: 0.177 AC: 7318 AN: 41454

American (AMR) AF: 0.260 AC: 3975 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 975 AN: 3464

East Asian (EAS) AF: 0.181 AC: 939 AN: 5174

South Asian (SAS) AF: 0.228 AC: 1096 AN: 4812

European-Finnish (FIN) AF: 0.333 AC: 3506 AN: 10538

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23483 AN: 67916

Other (OTH) AF: 0.301 AC: 637 AN: 2114

Alfa AF: 0.316 Hom.: 1019

Bravo AF: 0.271

Asia WGS AF: 0.223 AC: 773 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.62
PhyloP100		-0.60
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: rs12522395; hg19: chr5-90210518;