chr6-29440751-A-G

Variant names:

• chr6-29440751-A-G
• rs2074464
• NM_013941.4:c.736A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013941.4(OR10C1):​c.736A>G​(p.Met246Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,613,232 control chromosomes in the GnomAD database, including 254,968 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.57 (24919 hom., cov: 32)
  • Exomes 𝑓: 0.56 (230049 hom.)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.538

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.382627E-5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.736A>G	p.Met246Val	missense_variant	Exon 1 of 1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8764T>C		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.736A>G	p.Met246Val	missense_variant	Exon 1 of 1	6	NM_013941.4	ENSP00000419119.1
OR11A1	ENST00000377149.5	c.-388-8764T>C		intron_variant	Intron 1 of 4	6	NM_001394828.1	ENSP00000366354.1
OR10C1	ENST00000622521.1	c.742A>G	p.Met248Val	missense_variant	Exon 1 of 1	6		ENSP00000481429.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86603 AN: 151946 Hom.: 24888 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.543

GnomAD3 exomes AF: 0.563 AC: 140121 AN: 248988 Hom.: 39916 AF XY: 0.566 AC XY: 76450 AN XY: 134998

Gnomad AFR exome AF: 0.632

Gnomad AMR exome AF: 0.514

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.565

Gnomad SAS exome AF: 0.630

Gnomad FIN exome AF: 0.611

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.536

GnomAD4 exome AF: 0.559 AC: 816867 AN: 1461166 Hom.: 230049 Cov.: 43 AF XY: 0.560 AC XY: 407186 AN XY: 726912

Gnomad4 AFR exome AF: 0.635

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.509

Gnomad4 SAS exome AF: 0.632

Gnomad4 FIN exome AF: 0.606

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.551

GnomAD4 genome AF: 0.570 AC: 86685 AN: 152066 Hom.: 24919 Cov.: 32 AF XY: 0.572 AC XY: 42505 AN XY: 74312

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.548

Alfa AF: 0.545 Hom.: 40024

TwinsUK AF: 0.578 AC: 2142

ALSPAC AF: 0.555 AC: 2139

ESP6500AA AF: 0.685 AC: 2071

ESP6500EA AF: 0.550 AC: 2978

ExAC AF: 0.569 AC: 68863

EpiCase AF: 0.551

EpiControl AF: 0.548

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.0
DANN	Benign	0.79
DEOGEN2	Benign	0.00035	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0016	N
MetaRNN	Benign	0.000064	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-3.4	N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	2.6	N;.
REVEL	Benign	0.13
Sift	Benign	1.0	T;.
Polyphen		0.0	B;.
MPC		0.34
ClinPred		0.0070	T
GERP RS		3.5
Varity_R		0.052
gMVP		0.10

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

Other links and lift over

dbSNP: rs2074464; hg19: chr6-29408528; COSMIC: COSV65822967;