rs7313899

Variant names:

• chr12-55551335-A-G
• rs7313899
• NM_001005494.2:c.109A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005494.2(OR6C4):​c.109A>G​(p.Ile37Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,613,816 control chromosomes in the GnomAD database, including 785,806 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.99 (74906 hom., cov: 30)
  • Exomes 𝑓: 0.99 (710900 hom.)
• Consequence: OR6C4 NM_001005494.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 24 publications found

Genes affected

OR6C4 (HGNC:19632): (olfactory receptor family 6 subfamily C member 4) 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]

ENSG00000258763 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.8176448E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005494.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6C4	NM_001005494.2	MANE Select	c.109A>G	p.Ile37Val	missense	Exon 2 of 2	NP_001005494.1
	OR6C4	NM_001385975.1		c.109A>G	p.Ile37Val	missense	Exon 2 of 2	NP_001372904.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6C4	ENST00000641569.1	MANE Select	c.109A>G	p.Ile37Val	missense	Exon 2 of 2	ENSP00000493181.1
	OR6C4	ENST00000394256.2	TSL:6	c.109A>G	p.Ile37Val	missense	Exon 1 of 1	ENSP00000377799.2
	OR6C4	ENST00000641851.1		c.109A>G	p.Ile37Val	missense	Exon 2 of 2	ENSP00000493445.1

Frequencies

GnomAD3 genomes AF: 0.992 AC: 150902 AN: 152134 Hom.: 74847 Cov.: 30

Gnomad AFR AF: 0.997

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.998

GnomAD2 exomes AF: 0.992 AC: 248727 AN: 250632 AF XY: 0.993

Gnomad AFR exome AF: 0.997

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 0.999

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.993

Gnomad NFE exome AF: 0.986

Gnomad OTH exome AF: 0.993

GnomAD4 exome AF: 0.986 AC: 1441492 AN: 1461564 Hom.: 710900 Cov.: 42 AF XY: 0.987 AC XY: 717494 AN XY: 727102

African (AFR) AF: 0.998 AC: 33394 AN: 33460

American (AMR) AF: 0.996 AC: 44558 AN: 44718

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26115 AN: 26128

East Asian (EAS) AF: 1.00 AC: 39693 AN: 39694

South Asian (SAS) AF: 0.999 AC: 86171 AN: 86242

European-Finnish (FIN) AF: 0.993 AC: 53039 AN: 53414

Middle Eastern (MID) AF: 1.00 AC: 5762 AN: 5764

European-Non Finnish (NFE) AF: 0.983 AC: 1093020 AN: 1111762

Other (OTH) AF: 0.989 AC: 59740 AN: 60382

GnomAD4 genome AF: 0.992 AC: 151020 AN: 152252 Hom.: 74906 Cov.: 30 AF XY: 0.993 AC XY: 73907 AN XY: 74448

African (AFR) AF: 0.997 AC: 41436 AN: 41542

American (AMR) AF: 0.997 AC: 15235 AN: 15278

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 1.00 AC: 4818 AN: 4820

European-Finnish (FIN) AF: 0.995 AC: 10571 AN: 10622

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.985 AC: 67005 AN: 68022

Other (OTH) AF: 0.998 AC: 2108 AN: 2112

Alfa AF: 0.988 Hom.: 221153

Bravo AF: 0.992

TwinsUK AF: 0.982 AC: 3642

ALSPAC AF: 0.984 AC: 3793

ESP6500AA AF: 0.997 AC: 4391

ESP6500EA AF: 0.986 AC: 8480

ExAC AF: 0.992 AC: 120490

Asia WGS AF: 0.999 AC: 3473 AN: 3476

EpiCase AF: 0.988

EpiControl AF: 0.988

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.79
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.12	N
PhyloP100		-2.2
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.056
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.0017
ClinPred		0.0040	T
GERP RS		1.8
PromoterAI		0.0052	Neutral
Varity_R		0.028
gMVP		0.025
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: rs7313899; hg19: chr12-55945119; COSMIC: COSV107507027;