11-59477471-C-T

Variant names:

• chr11-59477471-C-T
• rs137857607
• NM_001004705.2:c.42C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001004705.2(OR4D10):​c.42C>T​(p.Phe14Phe) 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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4D10	NM_001004705.2	c.42C>T	p.Phe14Phe	synonymous_variant	Exon 3 of 3	ENST00000530162.2	NP_001004705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4D10	ENST00000530162.2	c.42C>T	p.Phe14Phe	synonymous_variant	Exon 3 of 3	6	NM_001004705.2	ENSP00000436424.1

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

GnomAD2 exomes AF: 0.00231 AC: 555 AN: 240120 AF XY: 0.00247

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 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

African (AFR) AF: 0.00148 AC: 49 AN: 33032

American (AMR) AF: 0.00177 AC: 76 AN: 43018

Ashkenazi Jewish (ASJ) AF: 0.00315 AC: 80 AN: 25430

East Asian (EAS) AF: 0.00 AC: 0 AN: 39558

South Asian (SAS) AF: 0.00163 AC: 137 AN: 84074

European-Finnish (FIN) AF: 0.000396 AC: 21 AN: 53030

Middle Eastern (MID) AF: 0.0175 AC: 100 AN: 5708

European-Non Finnish (NFE) AF: 0.00361 AC: 3992 AN: 1105846

Other (OTH) AF: 0.00317 AC: 190 AN: 59868

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

African (AFR) AF: 0.000987 AC: 41 AN: 41554

American (AMR) AF: 0.00196 AC: 30 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10606

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00399 AC: 271 AN: 68004

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

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

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-2.2
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs137857607; hg19: chr11-59244944;