rs28545014

Variant names:

• chr1-248349465-G-T
• rs28545014
• NM_001001918.1:c.691G>T

Variant summary

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

The NM_001001918.1(OR14C36):​c.691G>T​(p.Asp231Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,613,194 control chromosomes in the GnomAD database, including 242,214 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.50 (19768 hom., cov: 31)
  • Exomes 𝑓: 0.55 (222446 hom.)
• Consequence: OR14C36 NM_001001918.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 26 publications found

Genes affected

OR14C36 (HGNC:15026): (olfactory receptor family 14 subfamily C member 36) 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=1.3116002E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR14C36	NM_001001918.1	c.691G>T	p.Asp231Tyr	missense_variant	Exon 1 of 1	ENST00000317861.1	NP_001001918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR14C36	ENST00000317861.1	c.691G>T	p.Asp231Tyr	missense_variant	Exon 1 of 1	6	NM_001001918.1	ENSP00000324534.1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76550 AN: 151708 Hom.: 19760 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.519

GnomAD2 exomes AF: 0.525 AC: 131364 AN: 250396 AF XY: 0.533

Gnomad AFR exome AF: 0.393

Gnomad AMR exome AF: 0.467

Gnomad ASJ exome AF: 0.546

Gnomad EAS exome AF: 0.422

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.550 AC: 803694 AN: 1461368 Hom.: 222446 Cov.: 50 AF XY: 0.550 AC XY: 399768 AN XY: 727004

African (AFR) AF: 0.400 AC: 13399 AN: 33468

American (AMR) AF: 0.469 AC: 20944 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 14264 AN: 26126

East Asian (EAS) AF: 0.428 AC: 16986 AN: 39696

South Asian (SAS) AF: 0.530 AC: 45722 AN: 86238

European-Finnish (FIN) AF: 0.566 AC: 30204 AN: 53384

Middle Eastern (MID) AF: 0.554 AC: 3194 AN: 5766

European-Non Finnish (NFE) AF: 0.563 AC: 626056 AN: 1111608

Other (OTH) AF: 0.545 AC: 32925 AN: 60386

GnomAD4 genome AF: 0.505 AC: 76597 AN: 151826 Hom.: 19768 Cov.: 31 AF XY: 0.505 AC XY: 37508 AN XY: 74204

African (AFR) AF: 0.401 AC: 16611 AN: 41402

American (AMR) AF: 0.491 AC: 7493 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2183 AN: 5154

South Asian (SAS) AF: 0.540 AC: 2595 AN: 4808

European-Finnish (FIN) AF: 0.565 AC: 5949 AN: 10524

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37963 AN: 67908

Other (OTH) AF: 0.518 AC: 1092 AN: 2110

Alfa AF: 0.536 Hom.: 47233

Bravo AF: 0.495

TwinsUK AF: 0.556 AC: 2060

ALSPAC AF: 0.564 AC: 2175

ESP6500AA AF: 0.401 AC: 1768

ESP6500EA AF: 0.569 AC: 4894

ExAC AF: 0.526 AC: 63877

Asia WGS AF: 0.479 AC: 1662 AN: 3478

EpiCase AF: 0.558

EpiControl AF: 0.566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.00013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.12
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.082
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.079
MPC		0.70
ClinPred		0.022	T
GERP RS		1.6
Varity_R		0.68
gMVP		0.23
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28545014; hg19: chr1-248512767; COSMIC: COSV58600667;