5-90558750-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000508842.5(ADGRV1):c.34+29235G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 783,846 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (39 hom.)
• Consequence: ADGRV1 ENST00000508842.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.605

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-90558750-G-A is Benign according to our data. Variant chr5-90558750-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1210776.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00422 (642/152188) while in subpopulation SAS AF= 0.0147 (71/4824). AF 95% confidence interval is 0.012. There are 5 homozygotes in gnomad4. There are 323 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4			upstream_gene_variant		ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000508842.5	c.34+29235G>A		intron_variant		3
ADGRV1	ENST00000638316.1	n.65G>A		non_coding_transcript_exon_variant	1/6	5
ADGRV1	ENST00000405460.9			upstream_gene_variant		1	NM_032119.4	P1
ADGRV1	ENST00000640109.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 645 AN: 152070 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00722

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00201

Gnomad OTH AF: 0.00957

GnomAD3 exomes AF: 0.00602 AC: 866 AN: 143888 Hom.: 8 AF XY: 0.00695 AC XY: 537 AN XY: 77216

Gnomad AFR exome AF: 0.00710

Gnomad AMR exome AF: 0.00428

Gnomad ASJ exome AF: 0.0133

Gnomad EAS exome AF: 0.000185

Gnomad SAS exome AF: 0.0179

Gnomad FIN exome AF: 0.000127

Gnomad NFE exome AF: 0.00250

Gnomad OTH exome AF: 0.0102

GnomAD4 exome AF: 0.00451 AC: 2846 AN: 631658 Hom.: 39 Cov.: 8 AF XY: 0.00517 AC XY: 1745 AN XY: 337348

Gnomad4 AFR exome AF: 0.00684

Gnomad4 AMR exome AF: 0.00429

Gnomad4 ASJ exome AF: 0.0135

Gnomad4 EAS exome AF: 0.0000928

Gnomad4 SAS exome AF: 0.0167

Gnomad4 FIN exome AF: 0.000127

Gnomad4 NFE exome AF: 0.00215

Gnomad4 OTH exome AF: 0.00688

GnomAD4 genome AF: 0.00422 AC: 642 AN: 152188 Hom.: 5 Cov.: 32 AF XY: 0.00434 AC XY: 323 AN XY: 74424

Gnomad4 AFR AF: 0.00717

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00202

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00360 Hom.: 1

Bravo AF: 0.00418

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.8
Dann	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73176098; hg19: chr5-89854567;