rs1834026

Variant names:

• chr16-3204470-T-C
• rs1834026
• ENST00000304646.3:c.224T>C

Variant summary

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

The ENST00000304646.3(OR1F1):​c.224T>C​(p.Phe75Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,613,016 control chromosomes in the GnomAD database, including 162,520 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 0.42 (13629 hom., cov: 31)
  • Exomes 𝑓: 0.45 (148891 hom.)
• Consequence: OR1F1 ENST00000304646.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 34 publications found

Genes affected

OR1F1 (HGNC:8194): (olfactory receptor family 1 subfamily F 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=1.0714572E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR1F1	NM_001370639.4	c.224T>C	p.Phe75Ser	missense_variant	Exon 4 of 4		NP_001357568.2
OR1F1	NM_001370640.6	c.224T>C	p.Phe75Ser	missense_variant	Exon 4 of 4		NP_001357569.2
OR1F1	NM_001370641.2	c.224T>C	p.Phe75Ser	missense_variant	Exon 5 of 5		NP_001357570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR1F1	ENST00000304646.3	c.224T>C	p.Phe75Ser	missense_variant	Exon 4 of 4	6		ENSP00000305424.2
OR1F1	ENST00000576468.1	n.418+13133T>C		intron_variant	Intron 3 of 3	3
OR1F1	ENST00000652759.1	n.424-871T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62873 AN: 151464 Hom.: 13618 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.418

GnomAD2 exomes AF: 0.471 AC: 118517 AN: 251474 AF XY: 0.466

Gnomad AFR exome AF: 0.296

Gnomad AMR exome AF: 0.632

Gnomad ASJ exome AF: 0.464

Gnomad EAS exome AF: 0.595

Gnomad FIN exome AF: 0.408

Gnomad NFE exome AF: 0.446

Gnomad OTH exome AF: 0.448

GnomAD4 exome AF: 0.448 AC: 655250 AN: 1461434 Hom.: 148891 Cov.: 47 AF XY: 0.448 AC XY: 325714 AN XY: 727056

African (AFR) AF: 0.302 AC: 10033 AN: 33234

American (AMR) AF: 0.620 AC: 27705 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 12103 AN: 26134

East Asian (EAS) AF: 0.554 AC: 22000 AN: 39700

South Asian (SAS) AF: 0.447 AC: 38553 AN: 86256

European-Finnish (FIN) AF: 0.409 AC: 21853 AN: 53418

Middle Eastern (MID) AF: 0.426 AC: 2455 AN: 5764

European-Non Finnish (NFE) AF: 0.444 AC: 493710 AN: 1111854

Other (OTH) AF: 0.445 AC: 26838 AN: 60358

GnomAD4 genome AF: 0.415 AC: 62920 AN: 151582 Hom.: 13629 Cov.: 31 AF XY: 0.418 AC XY: 30980 AN XY: 74062

African (AFR) AF: 0.301 AC: 12383 AN: 41122

American (AMR) AF: 0.523 AC: 7976 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1614 AN: 3466

East Asian (EAS) AF: 0.577 AC: 2967 AN: 5146

South Asian (SAS) AF: 0.443 AC: 2130 AN: 4810

European-Finnish (FIN) AF: 0.397 AC: 4198 AN: 10566

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30304 AN: 67924

Other (OTH) AF: 0.417 AC: 876 AN: 2102

Alfa AF: 0.438 Hom.: 16375

Bravo AF: 0.420

TwinsUK AF: 0.451 AC: 1671

ALSPAC AF: 0.437 AC: 1683

ESP6500AA AF: 0.311 AC: 1368

ESP6500EA AF: 0.439 AC: 3775

ExAC AF: 0.462 AC: 56006

EpiCase AF: 0.439

EpiControl AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.66
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.064	T
MetaRNN	Benign	0.000011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-3.2	N
PhyloP100		1.5
PrimateAI	Benign	0.30	T
PROVEAN	Benign	5.2	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.039
MPC		0.0015
ClinPred		0.0022	T
GERP RS		4.3
PromoterAI		-0.0030	Neutral
Varity_R		0.051
gMVP		0.082
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1834026; hg19: chr16-3254470; COSMIC: COSV58960483;