16-3204911-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001370640.6(OR1F1):​c.665C>A​(p.Thr222Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

OR1F1
NM_001370640.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.919
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05998841).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR1F1NM_001370640.6 linkuse as main transcriptc.665C>A p.Thr222Asn missense_variant 4/4 ENST00000304646.3 NP_001357569.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR1F1ENST00000304646.3 linkuse as main transcriptc.665C>A p.Thr222Asn missense_variant 4/4 NM_001370640.6 ENSP00000305424 P1
OR1F1ENST00000576468.1 linkuse as main transcriptn.418+13574C>A intron_variant, non_coding_transcript_variant 3
OR1F1ENST00000652759.1 linkuse as main transcriptn.424-430C>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000279
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000147
AC:
37
AN:
251468
Hom.:
0
AF XY:
0.000155
AC XY:
21
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.0000924
Gnomad NFE exome
AF:
0.000290
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000162
AC:
237
AN:
1461890
Hom.:
0
Cov.:
48
AF XY:
0.000173
AC XY:
126
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
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:
0.0000374
Gnomad4 NFE exome
AF:
0.000207
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152280
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000279
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000230
Hom.:
0
Bravo
AF:
0.000147
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

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 submitterclinical testingAmbry GeneticsMay 18, 2022The c.665C>A (p.T222N) alteration is located in exon 1 (coding exon 1) of the OR1F1 gene. This alteration results from a C to A substitution at nucleotide position 665, causing the threonine (T) at amino acid position 222 to be replaced by an asparagine (N). 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
Benign
0.14
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
0.65
DANN
Benign
0.74
DEOGEN2
Benign
0.012
T
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.073
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.060
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.045
Sift
Benign
0.14
T
Sift4G
Benign
0.17
T
Polyphen
0.0010
B
Vest4
0.26
MVP
0.21
MPC
0.0021
ClinPred
0.023
T
GERP RS
2.0
Varity_R
0.24
gMVP
0.13

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

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

Other links and lift over

dbSNP: rs550163818; hg19: chr16-3254911; API