5-90725106-T-G

Variant names:

• chr5-90725106-T-G
• rs16869042
• NM_032119.4:c.9927T>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):​c.9927T>G​(p.Pro3309Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,533,190 control chromosomes in the GnomAD database, including 90,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8211 hom., cov: 32)
  • Exomes 𝑓: 0.34 (82065 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.0120
• Publications: 20 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: ClinGen, Orphanet
• Usher syndrome type 2C

  Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• febrile seizures, familial, 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

LOC105379077 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.017).
• BP6: Variant 5-90725106-T-G is Benign according to our data. Variant chr5-90725106-T-G is described in ClinVar as Benign. ClinVar VariationId is 46409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.012 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.473 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.9927T>G	p.Pro3309Pro	synonymous	Exon 47 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.9943T>G		non_coding_transcript_exon	Exon 47 of 90

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.9927T>G	p.Pro3309Pro	synonymous	Exon 47 of 90	ENSP00000384582.2
	ADGRV1	ENST00000509621.1	TSL:1	n.2624T>G		non_coding_transcript_exon	Exon 15 of 26
	ADGRV1	ENST00000640374.1	TSL:5	n.3071T>G		non_coding_transcript_exon	Exon 17 of 27

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48357 AN: 151878 Hom.: 8197 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.346 AC: 73643 AN: 212900 AF XY: 0.342

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.367

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.340 AC: 469218 AN: 1381196 Hom.: 82065 Cov.: 27 AF XY: 0.338 AC XY: 233051 AN XY: 689078

African (AFR) AF: 0.206 AC: 6250 AN: 30274

American (AMR) AF: 0.551 AC: 17125 AN: 31094

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 6815 AN: 24390

East Asian (EAS) AF: 0.436 AC: 16955 AN: 38888

South Asian (SAS) AF: 0.320 AC: 24707 AN: 77174

European-Finnish (FIN) AF: 0.339 AC: 17983 AN: 52970

Middle Eastern (MID) AF: 0.278 AC: 1537 AN: 5526

European-Non Finnish (NFE) AF: 0.337 AC: 358532 AN: 1063362

Other (OTH) AF: 0.336 AC: 19314 AN: 57518

GnomAD4 genome AF: 0.318 AC: 48376 AN: 151994 Hom.: 8211 Cov.: 32 AF XY: 0.321 AC XY: 23862 AN XY: 74286

African (AFR) AF: 0.219 AC: 9102 AN: 41500

American (AMR) AF: 0.482 AC: 7366 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1993 AN: 5160

South Asian (SAS) AF: 0.316 AC: 1525 AN: 4820

European-Finnish (FIN) AF: 0.333 AC: 3516 AN: 10550

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22741 AN: 67918

Other (OTH) AF: 0.351 AC: 740 AN: 2106

Alfa AF: 0.293 Hom.: 2974

Bravo AF: 0.333

Asia WGS AF: 0.339 AC: 1174 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Mar 23, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 07, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Genetic Services Laboratory, University of Chicago

Significance: Likely 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:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C Benign:1

Aug 11, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.8
DANN	Benign	0.66
PhyloP100		-0.012
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: rs16869042; hg19: chr5-90020923; COSMIC: COSV67980903;