16-3204470-T-C

Position:

• chr16-3204470-T-C

Variant summary

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

The NM_012360.3(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. 14/20 in silico tools predict 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 0.42 (13629 hom., cov: 31)
  • Exomes 𝑓: 0.45 (148891 hom.)
• Consequence: OR1F1 NM_012360.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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]

OR1F1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
OR1F1	NM_001370639.4	c.224T>C	p.Phe75Ser	missense_variant	4/4		NP_001357568.2
OR1F1	NM_001370640.6	c.224T>C	p.Phe75Ser	missense_variant	4/4		NP_001357569.2
OR1F1	NM_001370641.2	c.224T>C	p.Phe75Ser	missense_variant	5/5		NP_001357570.1

Ensembl

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

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

GnomAD3 exomes AF: 0.471 AC: 118517 AN: 251474 Hom.: 29102 AF XY: 0.466 AC XY: 63319 AN XY: 135910

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 SAS exome AF: 0.453

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

Gnomad4 AFR exome AF: 0.302

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.463

Gnomad4 EAS exome AF: 0.554

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.445

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

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.417

Alfa AF: 0.435 Hom.: 11166

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
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
Varity_R		0.051
gMVP		0.082

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

Publications

LitVar

Other links and lift over

dbSNP: rs1834026; hg19: chr16-3254470; COSMIC: COSV58960483;