chr5-90731463-T-A

Variant names:

• chr5-90731463-T-A
• rs2203825
• NM_032119.4:c.10549+1699T>A

Variant summary

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

The NM_032119.4(ADGRV1):​c.10549+1699T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,144 control chromosomes in the GnomAD database, including 3,592 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 0.13 (3592 hom., cov: 32)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• 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

LOC105379077 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 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.10549+1699T>A		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.10565+1699T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.10549+1699T>A		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.3246+1699T>A		intron	N/A
	ADGRV1	ENST00000639431.1	TSL:5	n.265+55254T>A		intron	N/A	ENSP00000491057.1	A0A1W2PNS5

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19285 AN: 152028 Hom.: 3573 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0400

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0357

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0904

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

GnomAD4 genome AF: 0.127 AC: 19349 AN: 152144 Hom.: 3592 Cov.: 32 AF XY: 0.124 AC XY: 9226 AN XY: 74388

African (AFR) AF: 0.409 AC: 16959 AN: 41462

American (AMR) AF: 0.0514 AC: 786 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 139 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0355 AC: 171 AN: 4814

European-Finnish (FIN) AF: 0.00471 AC: 50 AN: 10612

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0137 AC: 929 AN: 68006

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0817 Hom.: 279

Bravo AF: 0.143

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.0
DANN	Benign	0.68
PhyloP100		1.7
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: rs2203825; hg19: chr5-90027280;