14-18601318-T-A

Variant names:

• chr14-18601318-T-A
• rs141152619
• NM_001013354.1:c.202T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001013354.1(OR11H12):​c.202T>A​(p.Trp68Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,420,904 control chromosomes in the GnomAD database, including 7,478 homozygotes. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.034 (420 hom., cov: 20)
  • Exomes 𝑓: 0.027 (7058 hom.)
• Consequence: OR11H12 NM_001013354.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031088293).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

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.202T>A	p.Trp68Arg	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.202T>A	p.Trp68Arg	missense	Exon 1 of 1	ENSP00000449002.1	B2RN74
	ENSG00000306587	ENST00000819518.1		n.114+11261T>A		intron	N/A
	ENSG00000306587	ENST00000819519.1		n.188+1543T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 3727 AN: 111160 Hom.: 419 Cov.: 20

Gnomad AFR AF: 0.00792

Gnomad AMI AF: 0.00888

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0820

Gnomad EAS AF: 0.0489

Gnomad SAS AF: 0.0610

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0419

GnomAD2 exomes AF: 0.00761 AC: 1711 AN: 224770 AF XY: 0.00677

Gnomad AFR exome AF: 0.000824

Gnomad AMR exome AF: 0.0295

Gnomad ASJ exome AF: 0.00585

Gnomad EAS exome AF: 0.0120

Gnomad FIN exome AF: 0.000789

Gnomad NFE exome AF: 0.00377

Gnomad OTH exome AF: 0.00705

GnomAD4 exome AF: 0.0266 AC: 34900 AN: 1309678 Hom.: 7058 Cov.: 31 AF XY: 0.0273 AC XY: 17825 AN XY: 652240

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

African (AFR) AF: 0.00635 AC: 174 AN: 27414

American (AMR) AF: 0.129 AC: 4894 AN: 38014

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 1643 AN: 23004

East Asian (EAS) AF: 0.0449 AC: 1639 AN: 36480

South Asian (SAS) AF: 0.0519 AC: 4125 AN: 79478

European-Finnish (FIN) AF: 0.00547 AC: 267 AN: 48848

Middle Eastern (MID) AF: 0.0514 AC: 182 AN: 3542

European-Non Finnish (NFE) AF: 0.0203 AC: 20294 AN: 999406

Other (OTH) AF: 0.0314 AC: 1682 AN: 53492

⚠️ 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: 0.0335 AC: 3729 AN: 111226 Hom.: 420 Cov.: 20 AF XY: 0.0338 AC XY: 1839 AN XY: 54372

African (AFR) AF: 0.00790 AC: 207 AN: 26208

American (AMR) AF: 0.105 AC: 1210 AN: 11508

Ashkenazi Jewish (ASJ) AF: 0.0820 AC: 227 AN: 2768

East Asian (EAS) AF: 0.0493 AC: 192 AN: 3894

South Asian (SAS) AF: 0.0608 AC: 220 AN: 3616

European-Finnish (FIN) AF: 0.00377 AC: 31 AN: 8218

Middle Eastern (MID) AF: 0.0455 AC: 10 AN: 220

European-Non Finnish (NFE) AF: 0.0298 AC: 1564 AN: 52510

Other (OTH) AF: 0.0408 AC: 61 AN: 1496

Alfa AF: 0.0138 Hom.: 100

ExAC AF: 0.0107 AC: 1252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.53
DANN	Benign	0.26
DEOGEN2	Benign	0.00027	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.012	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.1	N
PhyloP100		-2.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	2.7	N
REVEL	Benign	0.047
Sift	Benign	0.47	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.022
MutPred		0.32		Gain of catalytic residue at T72 (P = 2e-04)
MPC		2.5
ClinPred		0.0021	T
GERP RS		-1.2
PromoterAI		-0.0016	Neutral
Varity_R		0.029
gMVP		0.020
Mutation Taster		=99/1	polymorphism (auto)

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: rs141152619; hg19: chr14-19377795;