rs7934354

Positions:

• chr11-5544676-A-G
• chr11-5544676-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005289.5(OR52H1):​c.830T>C​(p.Met277Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 1,613,792 control chromosomes in the GnomAD database, including 6,349 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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 0.077 (979 hom., cov: 32)
  • Exomes 𝑓: 0.040 (5370 hom.)
• Consequence: OR52H1 NM_001005289.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

Genes affected

OR52H1 (HGNC:15218): (olfactory receptor family 52 subfamily H 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040930808).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR52H1	NM_001005289.5	c.830T>C	p.Met277Thr	missense_variant	2/2	ENST00000322653.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR52H1	ENST00000322653.7	c.830T>C	p.Met277Thr	missense_variant	2/2		NM_001005289.5	P1
OR52H1	ENST00000641796.2	c.830T>C	p.Met277Thr	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.0774 AC: 11752 AN: 151898 Hom.: 979 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0670

GnomAD3 exomes AF: 0.0809 AC: 20330 AN: 251442 Hom.: 1926 AF XY: 0.0778 AC XY: 10572 AN XY: 135892

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.0361

Gnomad EAS exome AF: 0.360

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.0588

Gnomad NFE exome AF: 0.0186

Gnomad OTH exome AF: 0.0637

GnomAD4 exome AF: 0.0403 AC: 58886 AN: 1461776 Hom.: 5370 Cov.: 31 AF XY: 0.0419 AC XY: 30485 AN XY: 727206

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.0376

Gnomad4 EAS exome AF: 0.414

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.0549

Gnomad4 NFE exome AF: 0.0133

Gnomad4 OTH exome AF: 0.0595

GnomAD4 genome AF: 0.0774 AC: 11772 AN: 152016 Hom.: 979 Cov.: 32 AF XY: 0.0821 AC XY: 6099 AN XY: 74322

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0869

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.0161

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0333 Hom.: 659

Bravo AF: 0.0867

TwinsUK AF: 0.0105 AC: 39

ALSPAC AF: 0.0127 AC: 49

ESP6500AA AF: 0.139 AC: 611

ESP6500EA AF: 0.0199 AC: 171

ExAC AF: 0.0817 AC: 9918

Asia WGS AF: 0.252 AC: 874 AN: 3478

EpiCase AF: 0.0192

EpiControl AF: 0.0190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0095	T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.022
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.78	T;T
MetaRNN	Benign	0.0041	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.3	L;.
MutationTaster	Benign	1.1e-22	P;P
PrimateAI	Benign	0.21	T
Polyphen		0.46	P;.
MPC		0.027
ClinPred		0.058	T
GERP RS		5.2
Varity_R		0.69
gMVP		0.27

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: rs7934354; hg19: chr11-5565906; COSMIC: COSV59505476;