17-3397984-C-T

Variant names:

• chr17-3397984-C-T
• rs150989
• NM_003553.3:c.427G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003553.3(OR1E1):​c.427G>A​(p.Ala143Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,613,398 control chromosomes in the GnomAD database, including 714 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.021 (64 hom., cov: 32)
  • Exomes 𝑓: 0.028 (650 hom.)
• Consequence: OR1E1 NM_003553.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.00
• Publications: 10 publications found

Genes affected

OR1E1 (HGNC:8189): (olfactory receptor family 1 subfamily E member 1) 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012420684).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0208 (3159/151684) while in subpopulation NFE AF = 0.0322 (2189/68000). AF 95% confidence interval is 0.0311. There are 64 homozygotes in GnomAd4. There are 1378 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR1E1	NM_003553.3	c.427G>A	p.Ala143Thr	missense_variant	Exon 1 of 1	ENST00000322608.2	NP_003544.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR1E1	ENST00000322608.2	c.427G>A	p.Ala143Thr	missense_variant	Exon 1 of 1	6	NM_003553.3	ENSP00000313384.2

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3159 AN: 151568 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.00665

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00540

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0322

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.0208 AC: 5228 AN: 251100 AF XY: 0.0215

Gnomad AFR exome AF: 0.00602

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.00714

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0220

Gnomad NFE exome AF: 0.0334

Gnomad OTH exome AF: 0.0258

GnomAD4 exome AF: 0.0280 AC: 40996 AN: 1461714 Hom.: 650 Cov.: 31 AF XY: 0.0275 AC XY: 20009 AN XY: 727182

African (AFR) AF: 0.00492 AC: 164 AN: 33362

American (AMR) AF: 0.0152 AC: 679 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00704 AC: 184 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.00509 AC: 439 AN: 86254

European-Finnish (FIN) AF: 0.0212 AC: 1133 AN: 53420

Middle Eastern (MID) AF: 0.0170 AC: 98 AN: 5766

European-Non Finnish (NFE) AF: 0.0332 AC: 36887 AN: 1111986

Other (OTH) AF: 0.0233 AC: 1409 AN: 60382

GnomAD4 genome AF: 0.0208 AC: 3159 AN: 151684 Hom.: 64 Cov.: 32 AF XY: 0.0186 AC XY: 1378 AN XY: 74172

African (AFR) AF: 0.00663 AC: 272 AN: 41018

American (AMR) AF: 0.0166 AC: 253 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00540 AC: 26 AN: 4814

European-Finnish (FIN) AF: 0.0185 AC: 196 AN: 10600

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0322 AC: 2189 AN: 68000

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0158 Hom.: 4

Bravo AF: 0.0210

TwinsUK AF: 0.0345 AC: 128

ALSPAC AF: 0.0278 AC: 107

ESP6500AA AF: 0.00658 AC: 29

ESP6500EA AF: 0.0329 AC: 283

ExAC AF: 0.0215 AC: 2609

EpiCase AF: 0.0335

EpiControl AF: 0.0339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.057
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.18	N
PhyloP100		-4.0
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.055
Sift	Benign	0.088	T
Sift4G	Uncertain	0.026	D
Polyphen		0.013	B
Vest4		0.0060
MPC		0.32
ClinPred		0.013	T
GERP RS		-2.3
PromoterAI		-0.0078	Neutral
Varity_R		0.041
gMVP		0.077
Mutation Taster		=100/0	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: rs150989; hg19: chr17-3301278; COSMIC: COSV59459076;