11-6877383-C-T

Variant names:

• chr11-6877383-C-T
• rs16919049
• NM_207186.2:c.736C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_207186.2(OR10A4):​c.736C>T​(p.Leu246Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,614,136 control chromosomes in the GnomAD database, including 463 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (238 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (225 hom.)
• Consequence: OR10A4 NM_207186.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.969
• Publications: 8 publications found

Genes affected

OR10A4 (HGNC:15130): (olfactory receptor family 10 subfamily A 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]

ENSG00000283415 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018006861).
• BP6: Variant 11-6877383-C-T is Benign according to our data. Variant chr11-6877383-C-T is described in ClinVar as Benign. ClinVar VariationId is 782543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207186.2. 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
	OR10A4	NM_207186.2	MANE Select	c.736C>T	p.Leu246Phe	missense	Exon 1 of 1	NP_997069.2	Q9H209

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10A4	ENST00000379829.2	TSL:6 MANE Select	c.736C>T	p.Leu246Phe	missense	Exon 1 of 1	ENSP00000369157.2	Q9H209
	ENSG00000283415	ENST00000637205.2	TSL:5	n.606-26565G>A		intron	N/A
	ENSG00000283415	ENST00000767881.1		n.215-13083G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4713 AN: 152144 Hom.: 240 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0235

GnomAD2 exomes AF: 0.00792 AC: 1989 AN: 251178 AF XY: 0.00586

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.00468

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000335

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00308 AC: 4496 AN: 1461874 Hom.: 225 Cov.: 33 AF XY: 0.00265 AC XY: 1924 AN XY: 727240

African (AFR) AF: 0.109 AC: 3665 AN: 33474

American (AMR) AF: 0.00523 AC: 234 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00520 AC: 30 AN: 5768

European-Non Finnish (NFE) AF: 0.000143 AC: 159 AN: 1112006

Other (OTH) AF: 0.00628 AC: 379 AN: 60396

GnomAD4 genome AF: 0.0310 AC: 4720 AN: 152262 Hom.: 238 Cov.: 32 AF XY: 0.0301 AC XY: 2242 AN XY: 74450

African (AFR) AF: 0.108 AC: 4470 AN: 41526

American (AMR) AF: 0.0112 AC: 171 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68026

Other (OTH) AF: 0.0232 AC: 49 AN: 2110

Alfa AF: 0.0123 Hom.: 162

Bravo AF: 0.0353

ESP6500AA AF: 0.110 AC: 483

ESP6500EA AF: 0.000931 AC: 8

ExAC AF: 0.00998 AC: 1212

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000356

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
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.97
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.098
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.030	D
Polyphen		0.93	P
Vest4		0.22
MVP		0.58
MPC		0.12
ClinPred		0.031	T
GERP RS		3.4
Varity_R		0.43
gMVP		0.18
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16919049; hg19: chr11-6898614;