Variant chr16-3204280-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001370640.6(OR1F1):c.34T>C(p.Phe12Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,612,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

OR1F1
NM_001370640.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.30

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR1F1	NM_001370640.6 linkuse as main transcript	c.34T>C	p.Phe12Leu	missense_variant	4/4	ENST00000304646.3	NP_001357569.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
OR1F1	ENST00000304646.3 linkuse as main transcript	c.34T>C	p.Phe12Leu	missense_variant	4/4		NM_001370640.6	ENSP00000305424	P1
OR1F1	ENST00000576468.1 linkuse as main transcript	n.418+12943T>C		intron_variant, non_coding_transcript_variant		3
OR1F1	ENST00000652759.1 linkuse as main transcript	n.424-1061T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249814

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134898

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460022

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726050

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.34T>C (p.F12L) alteration is located in exon 1 (coding exon 1) of the OR1F1 gene. This alteration results from a T to C substitution at nucleotide position 34, causing the phenylalanine (F) at amino acid position 12 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

Eigen

Pathogenic

0.68

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

M_CAP

Benign

0.0045

MetaRNN

Pathogenic

0.90

MetaSVM

Benign

-0.85

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

0.57

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.24

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.68

MutPred

0.76

Gain of sheet (P = 0.0149);

MVP

0.68

MPC

0.0033

ClinPred

0.91

GERP RS

5.0

Varity_R

0.65

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over