rs10946991

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_013941.4(OR10C1):ā€‹c.762A>Cā€‹(p.Ala254=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0462 in 1,613,382 control chromosomes in the GnomAD database, including 3,737 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.098 ( 1350 hom., cov: 32)
Exomes š‘“: 0.041 ( 2387 hom. )

Consequence

OR10C1
NM_013941.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.87
Variant links:
Genes affected
OR10C1 (HGNC:8165): (olfactory receptor family 10 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]
OR11A1 (HGNC:8176): (olfactory receptor family 11 subfamily A 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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP7
Synonymous conserved (PhyloP=-1.87 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR10C1NM_013941.4 linkuse as main transcriptc.762A>C p.Ala254= synonymous_variant 1/1 ENST00000444197.3 NP_039229.3
OR11A1NM_001394828.1 linkuse as main transcriptc.-388-8790T>G intron_variant ENST00000377149.5 NP_001381757.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR10C1ENST00000444197.3 linkuse as main transcriptc.762A>C p.Ala254= synonymous_variant 1/1 NM_013941.4 ENSP00000419119 P1
OR11A1ENST00000377149.5 linkuse as main transcriptc.-388-8790T>G intron_variant NM_001394828.1 ENSP00000366354 P1
OR10C1ENST00000622521.1 linkuse as main transcriptc.768A>C p.Ala256= synonymous_variant 1/1 ENSP00000481429

Frequencies

GnomAD3 genomes
AF:
0.0977
AC:
14829
AN:
151794
Hom.:
1340
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.235
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0927
Gnomad ASJ
AF:
0.0968
Gnomad EAS
AF:
0.0771
Gnomad SAS
AF:
0.0590
Gnomad FIN
AF:
0.0181
Gnomad MID
AF:
0.0886
Gnomad NFE
AF:
0.0327
Gnomad OTH
AF:
0.115
GnomAD3 exomes
AF:
0.0555
AC:
13783
AN:
248482
Hom.:
761
AF XY:
0.0508
AC XY:
6853
AN XY:
134872
show subpopulations
Gnomad AFR exome
AF:
0.241
Gnomad AMR exome
AF:
0.0693
Gnomad ASJ exome
AF:
0.0938
Gnomad EAS exome
AF:
0.0505
Gnomad SAS exome
AF:
0.0466
Gnomad FIN exome
AF:
0.0210
Gnomad NFE exome
AF:
0.0319
Gnomad OTH exome
AF:
0.0587
GnomAD4 exome
AF:
0.0408
AC:
59689
AN:
1461470
Hom.:
2387
Cov.:
34
AF XY:
0.0407
AC XY:
29567
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.248
Gnomad4 AMR exome
AF:
0.0731
Gnomad4 ASJ exome
AF:
0.0936
Gnomad4 EAS exome
AF:
0.0825
Gnomad4 SAS exome
AF:
0.0471
Gnomad4 FIN exome
AF:
0.0196
Gnomad4 NFE exome
AF:
0.0297
Gnomad4 OTH exome
AF:
0.0596
GnomAD4 genome
AF:
0.0978
AC:
14863
AN:
151912
Hom.:
1350
Cov.:
32
AF XY:
0.0948
AC XY:
7034
AN XY:
74232
show subpopulations
Gnomad4 AFR
AF:
0.236
Gnomad4 AMR
AF:
0.0925
Gnomad4 ASJ
AF:
0.0968
Gnomad4 EAS
AF:
0.0765
Gnomad4 SAS
AF:
0.0582
Gnomad4 FIN
AF:
0.0181
Gnomad4 NFE
AF:
0.0327
Gnomad4 OTH
AF:
0.113
Alfa
AF:
0.0384
Hom.:
281
Bravo
AF:
0.110
Asia WGS
AF:
0.0760
AC:
265
AN:
3478
EpiCase
AF:
0.0370
EpiControl
AF:
0.0393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
6.0
DANN
Benign
0.75

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: rs10946991; hg19: chr6-29408554; COSMIC: COSV101010906; API