11-59477471-C-T

Variant summary

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

The NM_001004705.2(OR4D10):c.42C>T(p.Phe14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,601,830 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0032 (20 hom.)
• Consequence: OR4D10 NM_001004705.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.17

Genes affected

OR4D10 (HGNC:15173): (olfactory receptor family 4 subfamily D member 10) 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-59477471-C-T is Benign according to our data. Variant chr11-59477471-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2641812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.17 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR4D10	NM_001004705.2	c.42C>T	p.Phe14=	synonymous_variant	3/3	ENST00000530162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4D10	ENST00000530162.2	c.42C>T	p.Phe14=	synonymous_variant	3/3		NM_001004705.2	P1

Frequencies

GnomAD3 genomes AF: 0.00242 AC: 368 AN: 152148 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00398

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00231 AC: 555 AN: 240120 Hom.: 3 AF XY: 0.00247 AC XY: 321 AN XY: 130160

Gnomad AFR exome AF: 0.000521

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.00247

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00156

Gnomad FIN exome AF: 0.000333

Gnomad NFE exome AF: 0.00352

Gnomad OTH exome AF: 0.00499

GnomAD4 exome AF: 0.00320 AC: 4645 AN: 1449564 Hom.: 20 Cov.: 31 AF XY: 0.00325 AC XY: 2340 AN XY: 719964

Gnomad4 AFR exome AF: 0.00148

Gnomad4 AMR exome AF: 0.00177

Gnomad4 ASJ exome AF: 0.00315

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00163

Gnomad4 FIN exome AF: 0.000396

Gnomad4 NFE exome AF: 0.00361

Gnomad4 OTH exome AF: 0.00317

GnomAD4 genome AF: 0.00242 AC: 369 AN: 152266 Hom.: 2 Cov.: 31 AF XY: 0.00232 AC XY: 173 AN XY: 74460

Gnomad4 AFR AF: 0.000987

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00399

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00326 Hom.: 1

Bravo AF: 0.00260

Asia WGS AF: 0.00144 AC: 5 AN: 3478

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

OR4D10: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.1
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs137857607; hg19: chr11-59244944;