chr7-144074844-G-C

Variant names:

• chr7-144074844-G-C
• rs2961135
• NM_001386096.1:c.625G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386096.1(OR2A25):​c.625G>C​(p.Ala209Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,613,616 control chromosomes in the GnomAD database, including 229,993 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (25748 hom., cov: 31)
  • Exomes 𝑓: 0.53 (204245 hom.)
• Consequence: OR2A25 NM_001386096.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 30 publications found

Genes affected

OR2A25 (HGNC:19562): (olfactory receptor family 2 subfamily A member 25) 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.7080066E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386096.1. 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
	OR2A25	NM_001386096.1	MANE Select	c.625G>C	p.Ala209Pro	missense	Exon 2 of 2	NP_001373025.1
	OR2A25	NM_001004488.2		c.625G>C	p.Ala209Pro	missense	Exon 2 of 2	NP_001004488.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2A25	ENST00000641663.1	MANE Select	c.625G>C	p.Ala209Pro	missense	Exon 2 of 2	ENSP00000493343.1
	OR2A25	ENST00000408898.2	TSL:6	c.625G>C	p.Ala209Pro	missense	Exon 1 of 1	ENSP00000386167.2
	OR2A25	ENST00000641441.1		c.625G>C	p.Ala209Pro	missense	Exon 2 of 2	ENSP00000493159.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87415 AN: 151886 Hom.: 25712 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.577

GnomAD2 exomes AF: 0.570 AC: 142549 AN: 250024 AF XY: 0.558

Gnomad AFR exome AF: 0.691

Gnomad AMR exome AF: 0.744

Gnomad ASJ exome AF: 0.448

Gnomad EAS exome AF: 0.660

Gnomad FIN exome AF: 0.551

Gnomad NFE exome AF: 0.512

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.525 AC: 767701 AN: 1461612 Hom.: 204245 Cov.: 54 AF XY: 0.524 AC XY: 380853 AN XY: 727130

African (AFR) AF: 0.685 AC: 22931 AN: 33474

American (AMR) AF: 0.735 AC: 32868 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 11733 AN: 26132

East Asian (EAS) AF: 0.640 AC: 25405 AN: 39700

South Asian (SAS) AF: 0.526 AC: 45396 AN: 86254

European-Finnish (FIN) AF: 0.552 AC: 29476 AN: 53418

Middle Eastern (MID) AF: 0.498 AC: 2875 AN: 5768

European-Non Finnish (NFE) AF: 0.508 AC: 564500 AN: 1111752

Other (OTH) AF: 0.538 AC: 32517 AN: 60390

GnomAD4 genome AF: 0.576 AC: 87509 AN: 152004 Hom.: 25748 Cov.: 31 AF XY: 0.579 AC XY: 43027 AN XY: 74270

African (AFR) AF: 0.683 AC: 28316 AN: 41470

American (AMR) AF: 0.647 AC: 9891 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3470

East Asian (EAS) AF: 0.647 AC: 3335 AN: 5152

South Asian (SAS) AF: 0.526 AC: 2530 AN: 4808

European-Finnish (FIN) AF: 0.544 AC: 5739 AN: 10546

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34457 AN: 67964

Other (OTH) AF: 0.571 AC: 1206 AN: 2112

Alfa AF: 0.517 Hom.: 6627

Bravo AF: 0.594

TwinsUK AF: 0.504 AC: 1867

ALSPAC AF: 0.526 AC: 2026

ESP6500AA AF: 0.693 AC: 2856

ESP6500EA AF: 0.514 AC: 4345

ExAC AF: 0.566 AC: 68520

Asia WGS AF: 0.615 AC: 2142 AN: 3478

EpiCase AF: 0.505

EpiControl AF: 0.512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.2
DANN	Benign	0.47
DEOGEN2	Benign	0.00023	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.10	T
MetaRNN	Benign	0.0000027	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.3	N
PhyloP100		-0.19
PrimateAI	Benign	0.31	T
PROVEAN	Benign	7.3	N
REVEL	Benign	0.063
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.050
MPC		0.013
ClinPred		0.0032	T
GERP RS		4.8
Varity_R		0.091
gMVP		0.30
Mutation Taster		=99/1	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: rs2961135; hg19: chr7-143771937; COSMIC: COSV68717253; COSMIC: COSV68717253;