chr19-14799204-A-C

Variant summary

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

The NM_001370485.4(OR7C1):ā€‹c.933T>Gā€‹(p.Phe311Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,611,974 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000049 ( 0 hom. )

Consequence

OR7C1
NM_001370485.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.101
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 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=0.061692208).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR7C1NM_001370485.4 linkuse as main transcriptc.933T>G p.Phe311Leu missense_variant 5/5 ENST00000641666.2 NP_001357414.2
OR7C1NM_198944.1 linkuse as main transcriptc.933T>G p.Phe311Leu missense_variant 1/1 NP_945182.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR7C1ENST00000641666.2 linkuse as main transcriptc.933T>G p.Phe311Leu missense_variant 5/5 NM_001370485.4 ENSP00000493429 P1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152196
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000242
AC:
6
AN:
248270
Hom.:
0
AF XY:
0.0000298
AC XY:
4
AN XY:
134170
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000534
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000493
AC:
72
AN:
1459778
Hom.:
0
Cov.:
29
AF XY:
0.0000496
AC XY:
36
AN XY:
726214
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
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:
0.0000630
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74352
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:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000273
EpiControl
AF:
0.000237

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 GeneticsOct 05, 2023The c.933T>G (p.F311L) alteration is located in exon 1 (coding exon 1) of the OR7C1 gene. This alteration results from a T to G substitution at nucleotide position 933, causing the phenylalanine (F) at amino acid position 311 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
Benign
0.22
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.057
DANN
Benign
0.21
DEOGEN2
Benign
0.0022
T;T;T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0073
N
LIST_S2
Benign
0.18
.;.;.;T
M_CAP
Benign
0.00086
T
MetaRNN
Benign
0.062
T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-0.20
N;N;N;N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
0.060
.;.;.;N
REVEL
Benign
0.0030
Sift
Benign
0.54
.;.;.;T
Sift4G
Benign
0.36
.;.;.;T
Polyphen
0.0
B;B;B;B
Vest4
0.026
MutPred
0.40
Gain of MoRF binding (P = 0.0975);Gain of MoRF binding (P = 0.0975);Gain of MoRF binding (P = 0.0975);Gain of MoRF binding (P = 0.0975);
MVP
0.061
MPC
0.25
ClinPred
0.024
T
GERP RS
-1.4
Varity_R
0.034
gMVP
0.080

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.

Other links and lift over

dbSNP: rs549407154; hg19: chr19-14910016; API