chr1-248681658-T-C

Variant names:

• chr1-248681658-T-C
• rs55871516
• ENST00000695265.1:c.647A>G

Variant summary

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

The ENST00000695265.1(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.

• Frequency:
  • Genomes: 𝑓 0.14 (1473 hom., cov: 31)
  • Exomes 𝑓: 0.13 (5982 hom.)
• Consequence: OR14I1 ENST00000695265.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 16 publications found

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]

ENSG00000286015 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OR14I1	NM_001004734.4	c.647A>G	p.Tyr216Cys	missense_variant	Exon 5 of 5		NP_001004734.1
OR14I1	XM_047420643.1	c.647A>G	p.Tyr216Cys	missense_variant	Exon 3 of 3		XP_047276599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR14I1	ENST00000695265.1	c.647A>G	p.Tyr216Cys	missense_variant	Exon 5 of 5			ENSP00000511782.1
ENSG00000286015	ENST00000651827.1	c.*713A>G		3_prime_UTR_variant	Exon 5 of 5			ENSP00000498451.1
OR14I1	ENST00000342623.5	c.647A>G	p.Tyr216Cys	missense_variant	Exon 1 of 1	6		ENSP00000339726.3

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

GnomAD2 exomes AF: 0.140 AC: 35229 AN: 251432 AF XY: 0.139

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 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

African (AFR) AF: 0.158 AC: 2800 AN: 17694

American (AMR) AF: 0.146 AC: 6392 AN: 43740

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 2447 AN: 20984

East Asian (EAS) AF: 0.160 AC: 5776 AN: 36070

South Asian (SAS) AF: 0.148 AC: 10313 AN: 69796

European-Finnish (FIN) AF: 0.178 AC: 9480 AN: 53142

Middle Eastern (MID) AF: 0.0928 AC: 385 AN: 4148

European-Non Finnish (NFE) AF: 0.120 AC: 41864 AN: 350098

Other (OTH) AF: 0.119 AC: 3953 AN: 33096

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

African (AFR) AF: 0.160 AC: 6656 AN: 41484

American (AMR) AF: 0.104 AC: 1584 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3466

East Asian (EAS) AF: 0.161 AC: 833 AN: 5168

South Asian (SAS) AF: 0.147 AC: 708 AN: 4806

European-Finnish (FIN) AF: 0.191 AC: 2015 AN: 10560

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8149 AN: 67972

Other (OTH) AF: 0.0975 AC: 205 AN: 2102

Alfa AF: 0.124 Hom.: 2555

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
PhyloP100		4.1
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
Mutation Taster		=84/16	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: rs55871516; hg19: chr1-248844959; COSMIC: COSV61198975;