chr11-56542746-C-T

Position:

• chr11-56542746-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5M11	NM_001005245.1	c.512G>A	p.Ser171Asn	missense_variant	1/1	ENST00000528616.5	NP_001005245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5M11	ENST00000528616.5	c.512G>A	p.Ser171Asn	missense_variant	1/1	6	NM_001005245.1	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

GnomAD3 exomes AF: 0.748 AC: 185649 AN: 248234 Hom.: 70578 AF XY: 0.755 AC XY: 101695 AN XY: 134674

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 SAS exome AF: 0.825

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

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.795

Gnomad4 ASJ exome AF: 0.712

Gnomad4 EAS exome AF: 0.864

Gnomad4 SAS exome AF: 0.819

Gnomad4 FIN exome AF: 0.747

Gnomad4 NFE exome AF: 0.745

Gnomad4 OTH exome AF: 0.740

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

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.693

Alfa AF: 0.730 Hom.: 89537

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 v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs628524; hg19: chr11-56310222; COSMIC: COSV73141943;