rs11954387

Variant names:

• chr5-91006300-A-G
• rs11954387
• NM_032119.4:c.18152+20778A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-91006300-A-G
• chr5-91006300-A-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.18152+20778A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,102 control chromosomes in the GnomAD database, including 1,974 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 0.14 (1974 hom., cov: 32)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.18152+20778A>G		intron_variant	Intron 85 of 89	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.18152+20778A>G		intron_variant	Intron 85 of 89	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21018 AN: 151984 Hom.: 1972 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.138 AC: 21042 AN: 152102 Hom.: 1974 Cov.: 32 AF XY: 0.143 AC XY: 10635 AN XY: 74346

African (AFR) AF: 0.238 AC: 9888 AN: 41478

American (AMR) AF: 0.194 AC: 2961 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 340 AN: 3472

East Asian (EAS) AF: 0.226 AC: 1169 AN: 5174

South Asian (SAS) AF: 0.173 AC: 835 AN: 4818

European-Finnish (FIN) AF: 0.113 AC: 1196 AN: 10588

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0626 AC: 4257 AN: 68004

Other (OTH) AF: 0.150 AC: 316 AN: 2106

Alfa AF: 0.0882 Hom.: 489

Bravo AF: 0.149

Asia WGS AF: 0.201 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.7
DANN	Benign	0.74
PhyloP100		-0.26
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: rs11954387; hg19: chr5-90302117;