chr11-4946587-T-G

Position:

chr11-4946587-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005329.2(OR51A4):c.514A>C(p.Lys172Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000419 in 1,574,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

OR51A4
NM_001005329.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.87

Variant links:

Genes affected

OR51A4 (HGNC:14795): (olfactory receptor family 51 subfamily A member 4) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR51A4 links:

MMP26 (HGNC:14249): (matrix metallopeptidase 26) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

MMP26 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0213359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR51A4	NM_001005329.2 linkuse as main transcript	c.514A>C	p.Lys172Gln	missense_variant	2/2	ENST00000641898.1
MMP26	NM_021801.5 linkuse as main transcript	c.-144-41481T>G		intron_variant		ENST00000380390.6
MMP26	NM_001384608.1 linkuse as main transcript	c.-152-41683T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OR51A4	ENST00000641898.1 linkuse as main transcript	c.514A>C	p.Lys172Gln	missense_variant	2/2		NM_001005329.2	P1
MMP26	ENST00000380390.6 linkuse as main transcript	c.-144-41481T>G		intron_variant		5	NM_021801.5	P1
MMP26	ENST00000300762.2 linkuse as main transcript	c.-152-41683T>G		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

148808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000603

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000749

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000364

AC:

AN:

247068

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000351

AC:

AN:

1425110

Hom.:

Cov.:

AF XY:

0.0000366

AC XY:

AN XY:

710214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000389

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.000107

AC:

AN:

148924

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

72700

show subpopulations

Gnomad4 AFR

AF:

0.0000494

Gnomad4 AMR

AF:

0.000602

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000749

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000608

Hom.:

ExAC

AF:

0.0000414

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2021

The c.514A>C (p.K172Q) alteration is located in exon 1 (coding exon 1) of the OR51A4 gene. This alteration results from a A to C substitution at nucleotide position 514, causing the lysine (K) at amino acid position 172 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.18

DANN

Benign

0.77

DEOGEN2

Benign

0.0012

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.071

.;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.93

.;N

REVEL

Benign

0.010

Sift

Benign

0.57

.;T

Sift4G

Benign

0.45

.;T

Polyphen

0.0050

B;B

Vest4

0.062

MVP

0.33

MPC

0.46

ClinPred

0.017

GERP RS

-0.60

Varity_R

0.083

gMVP

0.086

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

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