11-4545481-C-T

Variant names:

• chr11-4545481-C-T
• rs2709182
• NM_001004137.1:c.291C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001004137.1(OR52M1):​c.291C>T​(p.Asp97Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 1,613,842 control chromosomes in the GnomAD database, including 198,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.49 (18262 hom., cov: 32)
  • Exomes 𝑓: 0.49 (180374 hom.)
• Consequence: OR52M1 NM_001004137.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.656
• Publications: 20 publications found

Genes affected

OR52M1 (HGNC:15225): (olfactory receptor family 52 subfamily M member 1) 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-4545481-C-T is Benign according to our data. Variant chr11-4545481-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060906.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.656 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004137.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52M1	NM_001004137.1	MANE Select	c.291C>T	p.Asp97Asp	synonymous	Exon 1 of 1	NP_001004137.1	Q8NGK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52M1	ENST00000360213.1	TSL:6 MANE Select	c.291C>T	p.Asp97Asp	synonymous	Exon 1 of 1	ENSP00000353343.1	Q8NGK5

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73868 AN: 151974 Hom.: 18253 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.500

GnomAD2 exomes AF: 0.451 AC: 113179 AN: 251038 AF XY: 0.462

Gnomad AFR exome AF: 0.508

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.612

Gnomad EAS exome AF: 0.282

Gnomad FIN exome AF: 0.454

Gnomad NFE exome AF: 0.502

Gnomad OTH exome AF: 0.472

GnomAD4 exome AF: 0.493 AC: 720375 AN: 1461750 Hom.: 180374 Cov.: 63 AF XY: 0.494 AC XY: 358887 AN XY: 727156

African (AFR) AF: 0.508 AC: 16993 AN: 33480

American (AMR) AF: 0.268 AC: 11980 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 15859 AN: 26136

East Asian (EAS) AF: 0.302 AC: 12006 AN: 39700

South Asian (SAS) AF: 0.491 AC: 42308 AN: 86238

European-Finnish (FIN) AF: 0.458 AC: 24465 AN: 53416

Middle Eastern (MID) AF: 0.534 AC: 3080 AN: 5764

European-Non Finnish (NFE) AF: 0.507 AC: 563899 AN: 1111900

Other (OTH) AF: 0.493 AC: 29785 AN: 60392

GnomAD4 genome AF: 0.486 AC: 73918 AN: 152092 Hom.: 18262 Cov.: 32 AF XY: 0.481 AC XY: 35755 AN XY: 74332

African (AFR) AF: 0.505 AC: 20934 AN: 41486

American (AMR) AF: 0.373 AC: 5707 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2138 AN: 3472

East Asian (EAS) AF: 0.295 AC: 1525 AN: 5178

South Asian (SAS) AF: 0.502 AC: 2417 AN: 4814

European-Finnish (FIN) AF: 0.469 AC: 4961 AN: 10570

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34549 AN: 67972

Other (OTH) AF: 0.500 AC: 1057 AN: 2114

Alfa AF: 0.460 Hom.: 26157

Bravo AF: 0.478

Asia WGS AF: 0.401 AC: 1394 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	OR52M1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.3
DANN	Benign	0.40
PhyloP100		-0.66
PromoterAI		-0.00050	Neutral
Mutation Taster		=100/0	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: rs2709182; hg19: chr11-4566711; COSMIC: COSV64172071;