chr6-131700654-C-A

Position:

chr6-131700654-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030908.2(OR2A4):c.748G>T(p.Val250Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000029 ( 15 hom. )

Failed GnomAD Quality Control

Consequence

OR2A4
NM_030908.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

Variant links:

Genes affected

OR2A4 (HGNC:14729): (olfactory receptor family 2 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]

OR2A4 links:

ENPP3 (HGNC:3358): (ectonucleotide pyrophosphatase/phosphodiesterase 3) The protein encoded by this gene belongs to a series of ectoenzymes that are involved in hydrolysis of extracellular nucleotides. These ectoenzymes possess ATPase and ATP pyrophosphatase activities and are type II transmembrane proteins. Expression of the related rat mRNA has been found in a subset of immature glial cells and in the alimentary tract. The corresponding rat protein has been detected in the pancreas, small intestine, colon, and liver. The human mRNA is expressed in glioma cells, prostate, and uterus. Expression of the human protein has been detected in uterus, basophils, and mast cells. Two transcript variants, one protein coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Oct 2015]

ENPP3 links:

ENPP3 (HGNC:):

ENPP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011495709).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2A4	NM_030908.2 linkuse as main transcript	c.748G>T	p.Val250Phe	missense_variant	1/1	ENST00000315453.4	NP_112170.1	O95047A0A126GVW2
ENPP3	NM_005021.5 linkuse as main transcript	c.1412+7030C>A		intron_variant		ENST00000357639.8	NP_005012.2	O14638

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR2A4	ENST00000315453.4 linkuse as main transcript	c.748G>T	p.Val250Phe	missense_variant	1/1	6	NM_030908.2	ENSP00000319546.2	O95047
ENPP3	ENST00000357639.8 linkuse as main transcript	c.1412+7030C>A		intron_variant		1	NM_005021.5	ENSP00000350265.3	O14638
ENPP3	ENST00000414305.5 linkuse as main transcript	c.1412+7030C>A		intron_variant		1		ENSP00000406261.1	O14638
ENPP3	ENST00000358229.6 linkuse as main transcript	c.1412+7030C>A		intron_variant		1		ENSP00000350964.5	F8W6H5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

133598

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000701

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000420

AC:

AN:

238092

Hom.:

AF XY:

0.0000618

AC XY:

AN XY:

129472

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.000128

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000288

AC:

AN:

1424164

Hom.:

Cov.:

AF XY:

0.0000339

AC XY:

AN XY:

708490

show subpopulations

Gnomad4 AFR exome

AF:

0.000723

Gnomad4 AMR exome

AF:

0.000148

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000245

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000546

Gnomad4 OTH exome

AF:

0.000154

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000224

AC:

AN:

133678

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

65218

show subpopulations

Gnomad4 AFR

AF:

0.0000699

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000875

Hom.:

ExAC

AF:

0.000284

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

Aug 02, 2021

The c.748G>T (p.V250F) alteration is located in exon 1 (coding exon 1) of the OR2A4 gene. This alteration results from a G to T substitution at nucleotide position 748, causing the valine (V) at amino acid position 250 to be replaced by a phenylalanine (F). 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

0.044

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.4

DANN

Benign

0.73

DEOGEN2

Benign

0.0034

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00029

LIST_S2

Benign

0.53

M_CAP

Benign

0.011

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-2.7

PrimateAI

Benign

0.41

PROVEAN

Benign

6.1

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.17

MVP

0.19

ClinPred

0.016

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.052

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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