11-56542746-C-T

Variant names:

• chr11-56542746-C-T
• rs628524
• NM_001005245.1:c.512G>A

Variant summary

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

The NM_001005245.1(OR5M11):​c.512G>A​(p.Ser171Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,613,138 control chromosomes in the GnomAD database, including 443,660 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 0.66 (34784 hom., cov: 31)
  • Exomes 𝑓: 0.75 (408876 hom.)
• Consequence: OR5M11 NM_001005245.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 29 publications found

Genes affected

OR5M11 (HGNC:15291): (olfactory receptor family 5 subfamily M member 11) 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=9.307166E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005245.1. 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
	OR5M11	NM_001005245.1	MANE Select	c.512G>A	p.Ser171Asn	missense	Exon 1 of 1	NP_001005245.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5M11	ENST00000528616.5	TSL:6 MANE Select	c.512G>A	p.Ser171Asn	missense	Exon 1 of 1	ENSP00000432417.2

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99893 AN: 151734 Hom.: 34770 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.688

GnomAD2 exomes AF: 0.748 AC: 185649 AN: 248234 AF XY: 0.755

Gnomad AFR exome AF: 0.403

Gnomad AMR exome AF: 0.801

Gnomad ASJ exome AF: 0.711

Gnomad EAS exome AF: 0.851

Gnomad FIN exome AF: 0.741

Gnomad NFE exome AF: 0.746

Gnomad OTH exome AF: 0.758

GnomAD4 exome AF: 0.745 AC: 1088726 AN: 1461282 Hom.: 408876 Cov.: 54 AF XY: 0.748 AC XY: 543900 AN XY: 726918

African (AFR) AF: 0.388 AC: 12988 AN: 33472

American (AMR) AF: 0.795 AC: 35473 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 18596 AN: 26132

East Asian (EAS) AF: 0.864 AC: 34303 AN: 39694

South Asian (SAS) AF: 0.819 AC: 70653 AN: 86240

European-Finnish (FIN) AF: 0.747 AC: 39881 AN: 53388

Middle Eastern (MID) AF: 0.722 AC: 4166 AN: 5768

European-Non Finnish (NFE) AF: 0.745 AC: 828035 AN: 1111616

Other (OTH) AF: 0.740 AC: 44631 AN: 60352

GnomAD4 genome AF: 0.658 AC: 99932 AN: 151856 Hom.: 34784 Cov.: 31 AF XY: 0.662 AC XY: 49134 AN XY: 74222

African (AFR) AF: 0.408 AC: 16892 AN: 41362

American (AMR) AF: 0.761 AC: 11617 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2430 AN: 3470

East Asian (EAS) AF: 0.856 AC: 4391 AN: 5132

South Asian (SAS) AF: 0.828 AC: 3985 AN: 4810

European-Finnish (FIN) AF: 0.734 AC: 7749 AN: 10558

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50549 AN: 67944

Other (OTH) AF: 0.693 AC: 1460 AN: 2108

Alfa AF: 0.716 Hom.: 131560

Bravo AF: 0.647

TwinsUK AF: 0.733 AC: 2718

ALSPAC AF: 0.739 AC: 2850

ESP6500AA AF: 0.440 AC: 1839

ESP6500EA AF: 0.748 AC: 6323

ExAC AF: 0.744 AC: 89976

Asia WGS AF: 0.831 AC: 2892 AN: 3478

EpiCase AF: 0.750

EpiControl AF: 0.749

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.14
DEOGEN2	Benign	0.00041	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.071	T
MetaRNN	Benign	9.3e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.2	N
PhyloP100		0.022
PrimateAI	Benign	0.27	T
PROVEAN	Benign	3.7	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.019
MPC		0.020
ClinPred		0.00055	T
GERP RS		4.0
Varity_R		0.038
gMVP		0.031
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: rs628524; hg19: chr11-56310222; COSMIC: COSV73141943;