chr11-4955427-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001004748.1(OR51A2):c.287C>A(p.Ser96Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,179,090 control chromosomes in the GnomAD database, including 5 homozygotes. 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 0.000019 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000020 ( 5 hom. )

Consequence

OR51A2
NM_001004748.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.306

Publications

1 publications found

Variant links:

Genes affected

OR51A2 (HGNC:14764): (olfactory receptor family 51 subfamily A member 2) 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]

OR51A2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07031551).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004748.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR51A2	NM_001004748.1	MANE Select	c.287C>A	p.Ser96Tyr	missense	Exon 1 of 1	NP_001004748.1	Q8NGJ7
MMP26	NM_021801.5	MANE Select	c.-144-32641G>T		intron	N/A	NP_068573.2	Q9NRE1
MMP26	NM_001384608.1		c.-152-32843G>T		intron	N/A	NP_001371537.1	A0A8J8YUH5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR51A2	ENST00000380371.1	TSL:6 MANE Select	c.287C>A	p.Ser96Tyr	missense	Exon 1 of 1	ENSP00000369729.1	Q8NGJ7
MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-144-32641G>T		intron	N/A	ENSP00000369753.1	Q9NRE1
MMP26	ENST00000300762.2	TSL:1	c.-152-32843G>T		intron	N/A	ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes

AF:

0.0000186

AC:

AN:

107712

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000547

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000377

AC:

AN:

185922

AF XY:

0.0000495

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000196

AC:

AN:

1071258

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

535186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27480

American (AMR)

AF:

0.00

AC:

AN:

31554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18754

East Asian (EAS)

AF:

0.00

AC:

AN:

25860

South Asian (SAS)

AF:

0.000282

AC:

AN:

74382

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

806056

Other (OTH)

AF:

0.00

AC:

AN:

44700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000185

AC:

AN:

107832

Hom.:

Cov.:

AF XY:

0.0000383

AC XY:

AN XY:

52198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32140

American (AMR)

AF:

0.00

AC:

AN:

9910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2380

East Asian (EAS)

AF:

0.00

AC:

AN:

3204

South Asian (SAS)

AF:

0.000547

AC:

AN:

3656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

47522

Other (OTH)

AF:

0.00

AC:

AN:

1442

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000936

Hom.:

ExAC

AF:

0.0000407

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.79

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.00089

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.090

M_CAP

Benign

0.0058

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.3

PhyloP100

-0.31

PROVEAN

Benign

0.64

REVEL

Benign

0.047

Sift

Benign

0.55

Sift4G

Benign

0.062

Polyphen

0.11

Vest4

0.15

MutPred

0.62

Loss of disorder (P = 0.026)

MVP

0.69

MPC

1.6

ClinPred

0.073

GERP RS

-0.081

PromoterAI

0.0090

Neutral

(source)

Varity_R

0.052

gMVP

0.28

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over