rs10946991

Variant names:

• chr6-29440777-A-C
• rs10946991
• NM_013941.4:c.762A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-29440777-A-C
• chr6-29440777-A-G
• chr6-29440777-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_013941.4(OR10C1):​c.762A>C​(p.Ala254Ala) 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: 𝑓 0.098 (1350 hom., cov: 32)
  • Exomes 𝑓: 0.041 (2387 hom.)
• Consequence: OR10C1 NM_013941.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.762A>C	p.Ala254Ala	synonymous_variant	Exon 1 of 1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8790T>G		intron_variant	Intron 1 of 4	ENST00000377149.5	NP_001381757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10C1	ENST00000444197.3	c.762A>C	p.Ala254Ala	synonymous_variant	Exon 1 of 1	6	NM_013941.4	ENSP00000419119.1
OR11A1	ENST00000377149.5	c.-388-8790T>G		intron_variant	Intron 1 of 4	6	NM_001394828.1	ENSP00000366354.1
OR10C1	ENST00000622521.1	c.768A>C	p.Ala256Ala	synonymous_variant	Exon 1 of 1	6		ENSP00000481429.1

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14829 AN: 151794 Hom.: 1340 Cov.: 32

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

GnomAD2 exomes AF: 0.0555 AC: 13783 AN: 248482 AF XY: 0.0508

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 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

African (AFR) AF: 0.248 AC: 8308 AN: 33464

American (AMR) AF: 0.0731 AC: 3267 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 2446 AN: 26132

East Asian (EAS) AF: 0.0825 AC: 3273 AN: 39690

South Asian (SAS) AF: 0.0471 AC: 4063 AN: 86236

European-Finnish (FIN) AF: 0.0196 AC: 1047 AN: 53378

Middle Eastern (MID) AF: 0.110 AC: 635 AN: 5760

European-Non Finnish (NFE) AF: 0.0297 AC: 33049 AN: 1111706

Other (OTH) AF: 0.0596 AC: 3601 AN: 60386

GnomAD4 genome AF: 0.0978 AC: 14863 AN: 151912 Hom.: 1350 Cov.: 32 AF XY: 0.0948 AC XY: 7034 AN XY: 74232

African (AFR) AF: 0.236 AC: 9759 AN: 41404

American (AMR) AF: 0.0925 AC: 1414 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3470

East Asian (EAS) AF: 0.0765 AC: 394 AN: 5148

South Asian (SAS) AF: 0.0582 AC: 280 AN: 4808

European-Finnish (FIN) AF: 0.0181 AC: 191 AN: 10552

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0327 AC: 2220 AN: 67930

Other (OTH) AF: 0.113 AC: 239 AN: 2108

Alfa AF: 0.0405 Hom.: 563

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
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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