chr14-19748048-G-C

Position:

• chr14-19748048-G-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.645G>C​(p.Leu215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 1,612,166 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (7 hom., cov: 36)
  • Exomes 𝑓: 0.0068 (81 hom.)
• Consequence: OR4Q3 NM_001405963.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.79

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=-0.9).
• BP6: Variant 14-19748048-G-C is Benign according to our data. Variant chr14-19748048-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2644035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.79 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR4Q3	NM_001405963.1	c.645G>C	p.Leu215=	synonymous_variant	2/2	ENST00000642117.2
OR4Q3	NM_172194.1	c.621G>C	p.Leu207=	synonymous_variant	1/1
OR4Q3	XM_024449618.1	c.810G>C	p.Leu270=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4Q3	ENST00000642117.2	c.645G>C	p.Leu215=	synonymous_variant	2/2		NM_001405963.1	P1
OR4N2	ENST00000557414.1	c.-303-13840G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00645 AC: 982 AN: 152162 Hom.: 7 Cov.: 36

Gnomad AFR AF: 0.000940

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00647

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00719 AC: 1802 AN: 250786 Hom.: 24 AF XY: 0.00724 AC XY: 981 AN XY: 135534

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.0440

Gnomad NFE exome AF: 0.00647

Gnomad OTH exome AF: 0.00817

GnomAD4 exome AF: 0.00678 AC: 9904 AN: 1459886 Hom.: 81 Cov.: 35 AF XY: 0.00660 AC XY: 4795 AN XY: 726312

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.000766

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.0390

Gnomad4 NFE exome AF: 0.00667

Gnomad4 OTH exome AF: 0.00514

GnomAD4 genome AF: 0.00645 AC: 982 AN: 152280 Hom.: 7 Cov.: 36 AF XY: 0.00782 AC XY: 582 AN XY: 74462

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0420

Gnomad4 NFE AF: 0.00647

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00525 Hom.: 2

EpiCase AF: 0.00606

EpiControl AF: 0.00534

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

Aug 01, 2022

OR4Q3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-20216207;