5-90706403-CTT-CTTT

Position:

• chr5-90706403-CTT-CTTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_032119.4(ADGRV1):​c.8730+21dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (35884 hom., cov: 0)
  • Exomes 𝑓: 0.45 (13569 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0450

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 -16 ACMG points.

• BP6: Variant 5-90706403-C-CT is Benign according to our data. Variant chr5-90706403-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 197047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.8730+21dup		intron_variant		ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.8730+21dup		intron_variant		1	NM_032119.4	ENSP00000384582	P1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 102421 AN: 146356 Hom.: 35860 Cov.: 0

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.708

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.450 AC: 545934 AN: 1213242 Hom.: 13569 Cov.: 25 AF XY: 0.449 AC XY: 269704 AN XY: 600146

Gnomad4 AFR exome AF: 0.495

Gnomad4 AMR exome AF: 0.448

Gnomad4 ASJ exome AF: 0.449

Gnomad4 EAS exome AF: 0.482

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.444

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.700 AC: 102477 AN: 146434 Hom.: 35884 Cov.: 0 AF XY: 0.700 AC XY: 49842 AN XY: 71218

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.711

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 21, 2019	- -

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 19, 2014	- -

Usher syndrome type 2C Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics, Royal Melbourne Hospital

Nov 20, 2020

Population allele frequency is 3% (rs60522638, 4,300/138,988 alleles, 1 homozygote in gnomAD v2.1). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1 -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs60522638; hg19: chr5-90002220;