11-4545229-CT-C

Variant names:

• chr11-4545229-CT-C
• rs77893620
• NM_001004137.1:c.41delT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001004137.1(OR52M1):​c.41delT​(p.Phe14SerfsTer32) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,612,378 control chromosomes in the GnomAD database, including 100 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0091 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (88 hom.)
• Consequence: OR52M1 NM_001004137.1 frameshift
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.22
• Publications: 5 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 -9 ACMG points.

• BP6: Variant 11-4545229-CT-C is Benign according to our data. Variant chr11-4545229-CT-C is described in ClinVar as Benign. ClinVar VariationId is 3055530.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00906 (1380/152284) while in subpopulation EAS AF = 0.0445 (230/5168). AF 95% confidence interval is 0.0398. There are 12 homozygotes in GnomAd4. There are 692 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

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.41delT	p.Phe14SerfsTer32	frameshift	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.41delT	p.Phe14SerfsTer32	frameshift	Exon 1 of 1	ENSP00000353343.1	Q8NGK5

Frequencies

GnomAD3 genomes AF: 0.00902 AC: 1373 AN: 152168 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.0212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00793 AC: 1975 AN: 248920 AF XY: 0.00814

Gnomad AFR exome AF: 0.0225

Gnomad AMR exome AF: 0.00221

Gnomad ASJ exome AF: 0.000203

Gnomad EAS exome AF: 0.0478

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000668

Gnomad OTH exome AF: 0.00511

GnomAD4 exome AF: 0.00354 AC: 5162 AN: 1460094 Hom.: 88 Cov.: 31 AF XY: 0.00400 AC XY: 2909 AN XY: 726346

African (AFR) AF: 0.0230 AC: 771 AN: 33450

American (AMR) AF: 0.00251 AC: 112 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.000193 AC: 5 AN: 25908

East Asian (EAS) AF: 0.0361 AC: 1432 AN: 39698

South Asian (SAS) AF: 0.0186 AC: 1597 AN: 85962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.00643 AC: 37 AN: 5754

European-Non Finnish (NFE) AF: 0.000671 AC: 745 AN: 1111108

Other (OTH) AF: 0.00767 AC: 463 AN: 60328

GnomAD4 genome AF: 0.00906 AC: 1380 AN: 152284 Hom.: 12 Cov.: 32 AF XY: 0.00929 AC XY: 692 AN XY: 74452

African (AFR) AF: 0.0218 AC: 906 AN: 41572

American (AMR) AF: 0.00523 AC: 80 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0445 AC: 230 AN: 5168

South Asian (SAS) AF: 0.0214 AC: 103 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68026

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00128 Hom.: 1

Bravo AF: 0.00976

Asia WGS AF: 0.0330 AC: 115 AN: 3478

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
PhyloP100		1.2
Mutation Taster		=136/64	polymorphism

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: rs77893620; hg19: chr11-4566459; COSMIC: COSV107466526;