chr14-18601137-G-T

Variant names:

• chr14-18601137-G-T
• rs200891589
• NM_001013354.1:c.21G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001013354.1(OR11H12):​c.21G>T​(p.Gln7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00027 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR11H12 NM_001013354.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.264
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.035033703).

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.21G>T	p.Gln7His	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.21G>T	p.Gln7His	missense	Exon 1 of 1	ENSP00000449002.1	B2RN74
	ENSG00000306587	ENST00000819518.1		n.114+11080G>T		intron	N/A
	ENSG00000306587	ENST00000819519.1		n.188+1362G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000719 AC: 100 AN: 139080 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000501

Gnomad ASJ AF: 0.000311

Gnomad EAS AF: 0.000211

Gnomad SAS AF: 0.00117

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00370

Gnomad NFE AF: 0.000444

Gnomad OTH AF: 0.000534

GnomAD2 exomes AF: 0.000301 AC: 34 AN: 112912 AF XY: 0.000257

Gnomad AFR exome AF: 0.000939

Gnomad AMR exome AF: 0.000323

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000971

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000372

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000270 AC: 375 AN: 1389094 Hom.: 2 Cov.: 25 AF XY: 0.000277 AC XY: 192 AN XY: 694278

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00141 AC: 44 AN: 31182

American (AMR) AF: 0.000544 AC: 24 AN: 44118

Ashkenazi Jewish (ASJ) AF: 0.000200 AC: 5 AN: 25040

East Asian (EAS) AF: 0.000203 AC: 8 AN: 39316

South Asian (SAS) AF: 0.000306 AC: 26 AN: 84850

European-Finnish (FIN) AF: 0.0000380 AC: 2 AN: 52686

Middle Eastern (MID) AF: 0.00103 AC: 4 AN: 3900

European-Non Finnish (NFE) AF: 0.000228 AC: 240 AN: 1050666

Other (OTH) AF: 0.000384 AC: 22 AN: 57336

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000718 AC: 100 AN: 139194 Hom.: 0 Cov.: 20 AF XY: 0.000692 AC XY: 47 AN XY: 67954

African (AFR) AF: 0.00151 AC: 56 AN: 37030

American (AMR) AF: 0.000500 AC: 7 AN: 13992

Ashkenazi Jewish (ASJ) AF: 0.000311 AC: 1 AN: 3220

East Asian (EAS) AF: 0.000211 AC: 1 AN: 4734

South Asian (SAS) AF: 0.00117 AC: 5 AN: 4272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9882

Middle Eastern (MID) AF: 0.00397 AC: 1 AN: 252

European-Non Finnish (NFE) AF: 0.000444 AC: 28 AN: 63048

Other (OTH) AF: 0.000527 AC: 1 AN: 1896

Alfa AF: 0.000397 Hom.: 0

ExAC AF: 0.000148 AC: 16

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.4
DANN	Benign	0.48
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.26	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.3	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.26
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.024
Sift	Benign	0.17	T
Sift4G	Benign	0.10	T
Polyphen		0.69	P
Vest4		0.12
MutPred		0.35		Gain of catalytic residue at V8 (P = 0)
MVP		0.40
MPC		2.3
ClinPred		0.011	T
PromoterAI		0.0083	Neutral
Varity_R		0.11
gMVP		0.095
Mutation Taster		=100/0	polymorphism

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: rs200891589; hg19: chr14-19377614;