5-91153214-T-C

Variant names:

• chr5-91153214-T-C
• rs7726023
• NM_032119.4:c.18625-7T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032119.4(ADGRV1):​c.18625-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 1,597,782 control chromosomes in the GnomAD database, including 695,135 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (63388 hom., cov: 30)
  • Exomes 𝑓: 0.93 (631747 hom.)
• Consequence: ADGRV1 NM_032119.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002895
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.172
• Publications: 11 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]

LUCAT1 (HGNC:48498): (lung cancer associated transcript 1)

LOC107986432 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-91153214-T-C is Benign according to our data. Variant chr5-91153214-T-C is described in ClinVar as Benign. ClinVar VariationId is 46299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.18625-7T>C		splice_region_variant, intron_variant	Intron 88 of 89	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.18625-7T>C		splice_region_variant, intron_variant	Intron 88 of 89	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138624 AN: 151996 Hom.: 63341 Cov.: 30

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.919

GnomAD2 exomes AF: 0.925 AC: 208936 AN: 225886 AF XY: 0.926

Gnomad AFR exome AF: 0.859

Gnomad AMR exome AF: 0.921

Gnomad ASJ exome AF: 0.935

Gnomad EAS exome AF: 0.895

Gnomad FIN exome AF: 0.927

Gnomad NFE exome AF: 0.936

Gnomad OTH exome AF: 0.926

GnomAD4 exome AF: 0.935 AC: 1351154 AN: 1445668 Hom.: 631747 Cov.: 37 AF XY: 0.935 AC XY: 670723 AN XY: 717512

African (AFR) AF: 0.863 AC: 28474 AN: 33000

American (AMR) AF: 0.921 AC: 39195 AN: 42550

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 24016 AN: 25776

East Asian (EAS) AF: 0.875 AC: 34130 AN: 39010

South Asian (SAS) AF: 0.936 AC: 78170 AN: 83540

European-Finnish (FIN) AF: 0.928 AC: 48682 AN: 52442

Middle Eastern (MID) AF: 0.914 AC: 5259 AN: 5752

European-Non Finnish (NFE) AF: 0.940 AC: 1037679 AN: 1103804

Other (OTH) AF: 0.929 AC: 55549 AN: 59794

GnomAD4 genome AF: 0.912 AC: 138724 AN: 152114 Hom.: 63388 Cov.: 30 AF XY: 0.912 AC XY: 67820 AN XY: 74360

African (AFR) AF: 0.862 AC: 35741 AN: 41480

American (AMR) AF: 0.924 AC: 14123 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3238 AN: 3472

East Asian (EAS) AF: 0.893 AC: 4583 AN: 5132

South Asian (SAS) AF: 0.927 AC: 4466 AN: 4818

European-Finnish (FIN) AF: 0.918 AC: 9736 AN: 10602

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63817 AN: 68006

Other (OTH) AF: 0.913 AC: 1925 AN: 2108

Alfa AF: 0.927 Hom.: 96490

Bravo AF: 0.909

Asia WGS AF: 0.865 AC: 3009 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 02, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Inferred frequency = 264/301 (LMM data) -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

Nov 29, 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

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 2C Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.29
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000029
dbscSNV1_RF	Benign	0.052
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: rs7726023; hg19: chr5-90449031;