11-124015839-A-C

Variant names:

• chr11-124015839-A-C
• rs199781271
• NM_001004462.2:c.265A>C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001004462.2(OR10G4):​c.265A>C​(p.Arg89Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0083 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR10G4 NM_001004462.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.288

Genes affected

OR10G4 (HGNC:14809): (olfactory receptor family 10 subfamily G 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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-124015839-A-C is Benign according to our data. Variant chr11-124015839-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642488.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.288 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10G4	NM_001004462.2	c.265A>C	p.Arg89Arg	synonymous_variant	Exon 2 of 2	ENST00000641722.1	NP_001004462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10G4	ENST00000641722.1	c.265A>C	p.Arg89Arg	synonymous_variant	Exon 2 of 2		NM_001004462.2	ENSP00000493036.1
OR10G4	ENST00000641521.1	c.265A>C	p.Arg89Arg	synonymous_variant	Exon 3 of 3			ENSP00000493354.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 38 AN: 148246 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000339

Gnomad ASJ AF: 0.000295

Gnomad EAS AF: 0.000396

Gnomad SAS AF: 0.00176

Gnomad FIN AF: 0.000295

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000272

Gnomad OTH AF: 0.000494

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00829 AC: 10317 AN: 1244700 Hom.: 0 Cov.: 46 AF XY: 0.00800 AC XY: 4981 AN XY: 622524

Gnomad4 AFR exome AF: 0.000490

Gnomad4 AMR exome AF: 0.00854

Gnomad4 ASJ exome AF: 0.00572

Gnomad4 EAS exome AF: 0.00332

Gnomad4 SAS exome AF: 0.00591

Gnomad4 FIN exome AF: 0.00556

Gnomad4 NFE exome AF: 0.00929

Gnomad4 OTH exome AF: 0.00641

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000249 AC: 37 AN: 148352 Hom.: 0 Cov.: 29 AF XY: 0.000277 AC XY: 20 AN XY: 72302

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000338

Gnomad4 ASJ AF: 0.000295

Gnomad4 EAS AF: 0.000397

Gnomad4 SAS AF: 0.00154

Gnomad4 FIN AF: 0.000295

Gnomad4 NFE AF: 0.000272

Gnomad4 OTH AF: 0.000489

Alfa AF: 0.0106 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OR10G4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.88
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs199781271; hg19: chr11-123886546; COSMIC: COSV57976602;