Variant 19-53267008-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173857.3(VN1R4):c.658A>G(p.Asn220Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,384,456 control chromosomes in the GnomAD database, including 70,198 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6736 hom., cov: 29)

Exomes 𝑓: 0.26 ( 63462 hom. )

Consequence

VN1R4
NM_173857.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.623

Variant links:

Genes affected

VN1R4 (HGNC:19871): (vomeronasal 1 receptor 4) Predicted to enable pheromone receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and response to pheromone. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

VN1R4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004701346).

BP6

Variant 19-53267008-T-C is Benign according to our data. Variant chr19-53267008-T-C is described in ClinVar as [Benign]. Clinvar id is 769464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VN1R4	NM_173857.3 linkuse as main transcript	c.658A>G	p.Asn220Asp	missense_variant	1/1	ENST00000311170.5	NP_776256.2	Q7Z5H5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VN1R4	ENST00000311170.5 linkuse as main transcript	c.658A>G	p.Asn220Asp	missense_variant	1/1	6	NM_173857.3	ENSP00000310856.4		Q7Z5H5

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

43771

AN:

148470

Hom.:

6737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.272

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.354

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.288

GnomAD3 exomes

AF:

0.239

AC:

49579

AN:

207406

Hom.:

8260

AF XY:

0.240

AC XY:

26780

AN XY:

111374

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.184

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.404

Gnomad SAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.219

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.260

AC:

321228

AN:

1235870

Hom.:

63462

Cov.:

AF XY:

0.261

AC XY:

161323

AN XY:

617498

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.333

Gnomad4 EAS exome

AF:

0.423

Gnomad4 SAS exome

AF:

0.291

Gnomad4 FIN exome

AF:

0.246

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.271

GnomAD4 genome

AF:

0.295

AC:

43785

AN:

148586

Hom.:

6736

Cov.:

AF XY:

0.292

AC XY:

21208

AN XY:

72538

show subpopulations

Gnomad4 AFR

AF:

0.268

Gnomad4 AMR

AF:

0.284

Gnomad4 ASJ

AF:

0.354

Gnomad4 EAS

AF:

0.429

Gnomad4 SAS

AF:

0.336

Gnomad4 FIN

AF:

0.256

Gnomad4 NFE

AF:

0.303

Gnomad4 OTH

AF:

0.287

Alfa

AF:

0.301

Hom.:

1607

Bravo

AF:

0.305

ExAC

AF:

0.235

AC:

28450

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.8

DANN

Benign

0.69

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0078

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.012

Sift

Benign

0.13

Sift4G

Benign

0.11

Vest4

0.13

MPC

0.33

ClinPred

0.014

GERP RS

-1.4

gMVP

0.039

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over