rs55871516

chr1-248681658-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004734.3(OR14I1):c.647A>G(p.Tyr216Cys) variant causes a missense change. The variant allele was found at a frequency of 0.133 in 780,800 control chromosomes in the GnomAD database, including 7,455 homozygotes. In-silico tool predicts 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1473 hom., cov: 31)
  • Exomes 𝑓: 0.13 (5982 hom.)
• Consequence: OR14I1 NM_001004734.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08

Genes affected

OR14I1 (HGNC:19575): (olfactory receptor family 14 subfamily I 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017676651).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR14I1	NM_001004734.3	c.647A>G	p.Tyr216Cys	missense_variant	5/5
OR14I1	XM_047420643.1	c.647A>G	p.Tyr216Cys	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR14I1	ENST00000342623.5	c.647A>G	p.Tyr216Cys	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20712 AN: 151914 Hom.: 1473 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0990

GnomAD3 exomes AF: 0.140 AC: 35229 AN: 251432 Hom.: 2645 AF XY: 0.139 AC XY: 18866 AN XY: 135888

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.146

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.133 AC: 83410 AN: 628768 Hom.: 5982 Cov.: 0 AF XY: 0.132 AC XY: 45343 AN XY: 342528

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.136 AC: 20720 AN: 152032 Hom.: 1473 Cov.: 31 AF XY: 0.139 AC XY: 10358 AN XY: 74318

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.0975

Alfa AF: 0.122 Hom.: 1774

Bravo AF: 0.131

TwinsUK AF: 0.115 AC: 428

ALSPAC AF: 0.113 AC: 436

ESP6500AA AF: 0.153 AC: 674

ESP6500EA AF: 0.115 AC: 992

ExAC AF: 0.139 AC: 16925

Asia WGS AF: 0.158 AC: 549 AN: 3478

EpiCase AF: 0.109

EpiControl AF: 0.115

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.7	H
MutationTaster	Benign	0.29	P
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-8.7	D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.16
MPC		0.25
ClinPred		0.070	T
GERP RS		3.5
Varity_R		0.83
gMVP		0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs55871516; hg19: chr1-248844959; COSMIC: COSV61198975;