rs115313932

Variant names:

• chr12-55331916-C-A
• rs115313932
• NM_001388498.1:c.216C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-55331916-C-A
• chr12-55331916-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001388498.1(OR6C3):​c.216C>A​(p.Thr72Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,613,980 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00086 (14 hom.)
• Consequence: OR6C3 NM_001388498.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.13
• Publications: 5 publications found

Genes affected

OR6C3 (HGNC:15437): (olfactory receptor family 6 subfamily C member 3) 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 12-55331916-C-A is Benign according to our data. Variant chr12-55331916-C-A is described in ClinVar as Benign. ClinVar VariationId is 791361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.13 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00579 (882/152304) while in subpopulation AFR AF = 0.0195 (809/41576). AF 95% confidence interval is 0.0183. There are 7 homozygotes in GnomAd4. There are 395 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388498.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6C3	NM_001388498.1	MANE Select	c.216C>A	p.Thr72Thr	synonymous	Exon 2 of 2	NP_001375427.1	Q9NZP0
	OR6C3	NM_054104.2		c.216C>A	p.Thr72Thr	synonymous	Exon 2 of 2	NP_473445.1	Q9NZP0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6C3	ENST00000641740.2	MANE Select	c.216C>A	p.Thr72Thr	synonymous	Exon 2 of 2	ENSP00000493380.1	Q9NZP0
	OR6C3	ENST00000641364.1		c.216C>A	p.Thr72Thr	synonymous	Exon 2 of 2	ENSP00000493034.1	Q9NZP0

Frequencies

GnomAD3 genomes AF: 0.00574 AC: 873 AN: 152186 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

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: 0.000323

Gnomad OTH AF: 0.00622

GnomAD2 exomes AF: 0.00202 AC: 506 AN: 250826 AF XY: 0.00153

Gnomad AFR exome AF: 0.0203

Gnomad AMR exome AF: 0.00315

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000309

Gnomad OTH exome AF: 0.00492

GnomAD4 exome AF: 0.000862 AC: 1260 AN: 1461676 Hom.: 14 Cov.: 32 AF XY: 0.000726 AC XY: 528 AN XY: 727160

African (AFR) AF: 0.0200 AC: 669 AN: 33470

American (AMR) AF: 0.00293 AC: 131 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5766

European-Non Finnish (NFE) AF: 0.000294 AC: 327 AN: 1111848

Other (OTH) AF: 0.00189 AC: 114 AN: 60384

GnomAD4 genome AF: 0.00579 AC: 882 AN: 152304 Hom.: 7 Cov.: 32 AF XY: 0.00530 AC XY: 395 AN XY: 74474

African (AFR) AF: 0.0195 AC: 809 AN: 41576

American (AMR) AF: 0.00248 AC: 38 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68030

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00193 Hom.: 2

Bravo AF: 0.00673

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.64
DANN	Benign	0.39
PhyloP100		-2.1
Mutation Taster		=99/1	polymorphism

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: rs115313932; hg19: chr12-55725700; COSMIC: COSV107488772;