chr5-90704137-T-C

Variant names:

• chr5-90704137-T-C
• rs10942605
• NM_032119.4:c.8287-252T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032119.4(ADGRV1):​c.8287-252T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,694 control chromosomes in the GnomAD database, including 33,496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (33496 hom., cov: 32)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.123
• 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: 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-90704137-T-C is Benign according to our data. Variant chr5-90704137-T-C is described in ClinVar as Benign. ClinVar VariationId is 1228117.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 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.8287-252T>C		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.8303-252T>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.8287-252T>C		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.984-252T>C		intron	N/A
	ADGRV1	ENST00000640403.1	TSL:5	c.5578-252T>C		intron	N/A	ENSP00000492531.1	A0A1W2PRC7

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99265 AN: 151576 Hom.: 33429 Cov.: 32

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.655 AC: 99393 AN: 151694 Hom.: 33496 Cov.: 32 AF XY: 0.658 AC XY: 48773 AN XY: 74116

African (AFR) AF: 0.797 AC: 32996 AN: 41422

American (AMR) AF: 0.714 AC: 10881 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2042 AN: 3468

East Asian (EAS) AF: 0.794 AC: 4080 AN: 5136

South Asian (SAS) AF: 0.598 AC: 2884 AN: 4820

European-Finnish (FIN) AF: 0.612 AC: 6410 AN: 10478

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37939 AN: 67824

Other (OTH) AF: 0.674 AC: 1421 AN: 2108

Alfa AF: 0.602 Hom.: 38068

Bravo AF: 0.678

Asia WGS AF: 0.745 AC: 2589 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.48
PhyloP100		-0.12
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: rs10942605; hg19: chr5-89999954;