chr14-18601123-C-A

Variant names:

• chr14-18601123-C-A
• rs749629107
• NM_001013354.1:c.7C>A

Variant summary

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

The NM_001013354.1(OR11H12):​c.7C>A​(p.Pro3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000078 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000053 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR11H12 NM_001013354.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.23
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031958073).

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.7C>A	p.Pro3Thr	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.7C>A	p.Pro3Thr	missense	Exon 1 of 1	ENSP00000449002.1	B2RN74
	ENSG00000306587	ENST00000819518.1		n.114+11066C>A		intron	N/A
	ENSG00000306587	ENST00000819519.1		n.188+1348C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000784 AC: 11 AN: 140264 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000550

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000716

Gnomad ASJ AF: 0.000302

Gnomad EAS AF: 0.000213

Gnomad SAS AF: 0.000233

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000619

Gnomad OTH AF: 0.000532

GnomAD2 exomes AF: 0.0000677 AC: 7 AN: 103418 AF XY: 0.0000753

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000412

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000533 AC: 74 AN: 1389486 Hom.: 1 Cov.: 24 AF XY: 0.0000503 AC XY: 35 AN XY: 695366

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

African (AFR) AF: 0.0000649 AC: 2 AN: 30798

American (AMR) AF: 0.000292 AC: 13 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.000312 AC: 8 AN: 25620

East Asian (EAS) AF: 0.0000762 AC: 3 AN: 39366

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 84960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3936

European-Non Finnish (NFE) AF: 0.0000372 AC: 39 AN: 1049330

Other (OTH) AF: 0.000121 AC: 7 AN: 57696

⚠️ 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: 0.0000784 AC: 11 AN: 140368 Hom.: 0 Cov.: 19 AF XY: 0.0000440 AC XY: 3 AN XY: 68114

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

African (AFR) AF: 0.0000549 AC: 2 AN: 36454

American (AMR) AF: 0.0000715 AC: 1 AN: 13978

Ashkenazi Jewish (ASJ) AF: 0.000302 AC: 1 AN: 3310

East Asian (EAS) AF: 0.000213 AC: 1 AN: 4694

South Asian (SAS) AF: 0.000233 AC: 1 AN: 4294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.0000619 AC: 4 AN: 64622

Other (OTH) AF: 0.000528 AC: 1 AN: 1894

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000766284), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000961 Hom.: 0

ExAC AF: 0.0000377 AC: 4

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	0.072
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.5
DANN	Benign	0.44
DEOGEN2	Benign	0.00022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.2
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.033
Sift	Benign	0.44	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.35		Gain of catalytic residue at V8 (P = 0)
MVP		0.35
MPC		1.8
ClinPred		0.027	T
PromoterAI		0.010	Neutral
Varity_R		0.035
gMVP		0.058
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: rs749629107; hg19: chr14-19377600;