chr19-14799455-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370485.4(OR7C1):​c.682A>T​(p.Ile228Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,613,968 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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: 0.00013 ( 1 hom. )

Consequence

OR7C1
NM_001370485.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.468
Variant links:
Genes affected
OR7C1 (HGNC:8373): (olfactory receptor family 7 subfamily C 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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR7C1NM_001370485.4 linkuse as main transcriptc.682A>T p.Ile228Phe missense_variant 5/5 ENST00000641666.2
OR7C1NM_198944.1 linkuse as main transcriptc.682A>T p.Ile228Phe missense_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR7C1ENST00000641666.2 linkuse as main transcriptc.682A>T p.Ile228Phe missense_variant 5/5 NM_001370485.4 P1

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000836
AC:
21
AN:
251204
Hom.:
0
AF XY:
0.0000663
AC XY:
9
AN XY:
135782
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00129
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000134
AC:
196
AN:
1461884
Hom.:
1
Cov.:
32
AF XY:
0.000127
AC XY:
92
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000842
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000153
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152084
Hom.:
0
Cov.:
32
AF XY:
0.0000539
AC XY:
4
AN XY:
74276
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000179
Hom.:
0
Bravo
AF:
0.000113
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000218
EpiControl
AF:
0.0000593

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 GeneticsJan 16, 2024The c.682A>T (p.I228F) alteration is located in exon 1 (coding exon 1) of the OR7C1 gene. This alteration results from a A to T substitution at nucleotide position 682, causing the isoleucine (I) at amino acid position 228 to be replaced by a phenylalanine (F). 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
0.095
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
20
DANN
Benign
0.93
DEOGEN2
Benign
0.0073
T;T;T;T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.76
.;.;.;T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.092
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.9
M;M;M;M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.25
T
PROVEAN
Uncertain
-3.5
.;.;.;D
REVEL
Benign
0.060
Sift
Uncertain
0.0010
.;.;.;D
Sift4G
Uncertain
0.0060
.;.;.;D
Polyphen
0.99
D;D;D;D
Vest4
0.32
MVP
0.15
MPC
0.95
ClinPred
0.30
T
GERP RS
1.5
Varity_R
0.40
gMVP
0.070

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.23
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.23
Position offset: 1

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: rs202114966; hg19: chr19-14910267; API