5-90745274-A-G

Variant names:

• chr5-90745274-A-G
• rs116184119
• NM_032119.4:c.10769+9A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032119.4(ADGRV1):​c.10769+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00788 in 1,540,212 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0080 (45 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.387

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-90745274-A-G is Benign according to our data. Variant chr5-90745274-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 46251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90745274-A-G is described in Lovd as [Benign]. Variant chr5-90745274-A-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0063 (959/152284) while in subpopulation AMR AF= 0.0105 (161/15294). AF 95% confidence interval is 0.0092. There are 6 homozygotes in gnomad4. There are 446 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.10769+9A>G		intron_variant	Intron 51 of 89	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.10769+9A>G		intron_variant	Intron 51 of 89	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.00630 AC: 959 AN: 152166 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00882

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00685 AC: 1472 AN: 214876 Hom.: 9 AF XY: 0.00705 AC XY: 828 AN XY: 117422

Gnomad AFR exome AF: 0.000807

Gnomad AMR exome AF: 0.00583

Gnomad ASJ exome AF: 0.0308

Gnomad EAS exome AF: 0.0000604

Gnomad SAS exome AF: 0.00194

Gnomad FIN exome AF: 0.00254

Gnomad NFE exome AF: 0.00903

Gnomad OTH exome AF: 0.00469

GnomAD4 exome AF: 0.00805 AC: 11171 AN: 1387928 Hom.: 45 Cov.: 22 AF XY: 0.00801 AC XY: 5517 AN XY: 689056

Gnomad4 AFR exome AF: 0.000957

Gnomad4 AMR exome AF: 0.00582

Gnomad4 ASJ exome AF: 0.0252

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00225

Gnomad4 FIN exome AF: 0.00301

Gnomad4 NFE exome AF: 0.00886

Gnomad4 OTH exome AF: 0.00850

GnomAD4 genome AF: 0.00630 AC: 959 AN: 152284 Hom.: 6 Cov.: 32 AF XY: 0.00599 AC XY: 446 AN XY: 74462

Gnomad4 AFR AF: 0.00144

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00882

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00648 Hom.: 2

Bravo AF: 0.00645

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:7

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ADGRV1: BS2 -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 20, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 02, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:5

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 26, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

10769+9A>G in intron 51 of GPR98: This variant is not expected to have clinical significance because it has been identified in 82/6550 (1.25%) European American chromosomes from a broad, though clinically unspecified population (NHLBI Exom e Sequencing Project; http://evs.gs.washington.edu/EVS; rs116184119). -

Usher syndrome type 2C Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116184119; hg19: chr5-90041091;