chr14-19747770-T-C

Position:

• chr14-19747770-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001405963.1(OR4Q3):​c.367T>C​(p.Leu123Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,612,958 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 36)
  • Exomes 𝑓: 0.0037 (14 hom.)
• Consequence: OR4Q3 NM_001405963.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.963

Genes affected

OR4Q3 (HGNC:15426): (olfactory receptor family 4 subfamily Q member 3) 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]

OR4N2 (HGNC:14742): (olfactory receptor family 4 subfamily N member 2) 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 seven-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, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 14-19747770-T-C is Benign according to our data. Variant chr14-19747770-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2644034.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.963 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4Q3	NM_001405963.1	c.367T>C	p.Leu123Leu	synonymous_variant	2/2		NP_001392892.1
OR4Q3	NM_172194.1	c.343T>C	p.Leu115Leu	synonymous_variant	1/1		NP_751944.1
OR4Q3	XM_024449618.1	c.532T>C	p.Leu178Leu	synonymous_variant	3/4		XP_024305386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4Q3	ENST00000642117.2	c.367T>C	p.Leu123Leu	synonymous_variant	2/2			ENSP00000492928.2
OR4N2	ENST00000557414.1	c.-303-14118T>C		intron_variant		6		ENSP00000451462.1

Frequencies

GnomAD3 genomes AF: 0.00273 AC: 416 AN: 152206 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00498

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00293 AC: 736 AN: 250880 Hom.: 2 AF XY: 0.00294 AC XY: 399 AN XY: 135618

Gnomad AFR exome AF: 0.000679

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.00564

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00372 AC: 5435 AN: 1460634 Hom.: 14 Cov.: 32 AF XY: 0.00359 AC XY: 2605 AN XY: 726560

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.00197

Gnomad4 NFE exome AF: 0.00453

Gnomad4 OTH exome AF: 0.00312

GnomAD4 genome AF: 0.00272 AC: 415 AN: 152324 Hom.: 0 Cov.: 36 AF XY: 0.00228 AC XY: 170 AN XY: 74490

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00216

Gnomad4 NFE AF: 0.00499

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00374 Hom.: 0

Bravo AF: 0.00275

EpiCase AF: 0.00420

EpiControl AF: 0.00575

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

OR4Q3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-20215929; COSMIC: COSV59181076;