14-18601348-C-G

Variant names:

• chr14-18601348-C-G
• rs1220555775
• NM_001013354.1:c.232C>G

Variant summary

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

The NM_001013354.1(OR11H12):​c.232C>G​(p.Leu78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,420,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L78M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OR11H12 NM_001013354.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 0 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=0.31998736).

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.232C>G	p.Leu78Val	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.232C>G	p.Leu78Val	missense	Exon 1 of 1	ENSP00000449002.1	B2RN74
	ENSG00000306587	ENST00000819518.1		n.114+11291C>G		intron	N/A
	ENSG00000306587	ENST00000819519.1		n.188+1573C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1420020 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 707456

African (AFR) AF: 0.00 AC: 0 AN: 30480

American (AMR) AF: 0.00 AC: 0 AN: 44188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25720

East Asian (EAS) AF: 0.00 AC: 0 AN: 39378

South Asian (SAS) AF: 0.00 AC: 0 AN: 85148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3976

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1079422

Other (OTH) AF: 0.00 AC: 0 AN: 58692

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.088
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.092	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.12
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.060
Sift	Benign	0.095	T
Sift4G	Uncertain	0.055	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.36		Gain of catalytic residue at N80 (P = 4e-04)
MVP		0.57
MPC		3.1
ClinPred		0.54	D
GERP RS		0.58
PromoterAI		-0.0088	Neutral
Varity_R		0.11
gMVP		0.015
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1220555775; hg19: chr14-19377825;