11-6877558-G-A

Position:

• chr11-6877558-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_207186.2(OR10A4):​c.911G>A​(p.Arg304Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,613,892 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (33 hom.)
• Consequence: OR10A4 NM_207186.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00600

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038343966).
• BP6: Variant 11-6877558-G-A is Benign according to our data. Variant chr11-6877558-G-A is described in ClinVar as [Benign]. Clinvar id is 774689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10A4	NM_207186.2	c.911G>A	p.Arg304Gln	missense_variant	1/1	ENST00000379829.2	NP_997069.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10A4	ENST00000379829.2	c.911G>A	p.Arg304Gln	missense_variant	1/1		NM_207186.2	ENSP00000369157	P1
	ENST00000637205.2	n.606-26740C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 344 AN: 152146 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00298

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00364 AC: 912 AN: 250532 Hom.: 8 AF XY: 0.00424 AC XY: 574 AN XY: 135370

Gnomad AFR exome AF: 0.000556

Gnomad AMR exome AF: 0.00295

Gnomad ASJ exome AF: 0.00688

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0130

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00272

Gnomad OTH exome AF: 0.00344

GnomAD4 exome AF: 0.00320 AC: 4683 AN: 1461628 Hom.: 33 Cov.: 33 AF XY: 0.00363 AC XY: 2640 AN XY: 727092

Gnomad4 AFR exome AF: 0.000627

Gnomad4 AMR exome AF: 0.00302

Gnomad4 ASJ exome AF: 0.00754

Gnomad4 EAS exome AF: 0.00340

Gnomad4 SAS exome AF: 0.0133

Gnomad4 FIN exome AF: 0.000168

Gnomad4 NFE exome AF: 0.00243

Gnomad4 OTH exome AF: 0.00455

GnomAD4 genome AF: 0.00227 AC: 345 AN: 152264 Hom.: 5 Cov.: 32 AF XY: 0.00228 AC XY: 170 AN XY: 74434

Gnomad4 AFR AF: 0.000506

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00298

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00281 Hom.: 1

Bravo AF: 0.00210

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00291 AC: 25

ExAC AF: 0.00373 AC: 453

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00300

EpiControl AF: 0.00326

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.078
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.028	D
Polyphen		0.032	B
Vest4		0.21
MVP		0.55
MPC		0.018
ClinPred		0.031	T
GERP RS		4.0
Varity_R		0.20
gMVP		0.19

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: rs140094304; hg19: chr11-6898789; COSMIC: COSV65841843; COSMIC: COSV65841843;