rs201865883

Variant names:

• chr14-18601262-C-G
• rs201865883
• NM_001013354.1:c.146C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-18601262-C-G
• chr14-18601262-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001013354.1(OR11H12):​c.146C>G​(p.Thr49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000997 in 1,604,674 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T49I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: OR11H12 NM_001013354.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 2 publications found

Genes affected

OR11H12 (HGNC:30738): (olfactory receptor family 11 subfamily H member 12) 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]

ENSG00000306587 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2949863).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013354.1. 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
	OR11H12	NM_001013354.1	MANE Select	c.146C>G	p.Thr49Arg	missense	Exon 1 of 1	NP_001013372.1	B2RN74

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR11H12	ENST00000550708.2	TSL:6 MANE Select	c.146C>G	p.Thr49Arg	missense	Exon 1 of 1	ENSP00000449002.1	B2RN74
	ENSG00000306587	ENST00000819518.1		n.114+11205C>G		intron	N/A
	ENSG00000306587	ENST00000819519.1		n.188+1487C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000137 AC: 2 AN: 145704 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000299

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 249220 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000960 AC: 14 AN: 1458970 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 725854

African (AFR) AF: 0.00 AC: 0 AN: 33198

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111396

Other (OTH) AF: 0.00 AC: 0 AN: 60172

GnomAD4 genome AF: 0.0000137 AC: 2 AN: 145704 Hom.: 0 Cov.: 20 AF XY: 0.0000141 AC XY: 1 AN XY: 70970

African (AFR) AF: 0.00 AC: 0 AN: 37590

American (AMR) AF: 0.00 AC: 0 AN: 14662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 4990

South Asian (SAS) AF: 0.00 AC: 0 AN: 4652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000299 AC: 2 AN: 66916

Other (OTH) AF: 0.00 AC: 0 AN: 1978

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000168 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.076
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.047
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.89	P
Vest4		0.17
MutPred		0.64		Gain of catalytic residue at L45 (P = 0)
MVP		0.24
MPC		2.2
ClinPred		0.24	T
PromoterAI		0.0029	Neutral
Varity_R		0.41
gMVP		0.23
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs201865883; hg19: chr14-19377739;