11-48307092-C-T

Variant names:

• chr11-48307092-C-T
• rs753095
• NM_001004725.1:c.870C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001004725.1(OR4S1):​c.870C>T​(p.Asn290Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,612,636 control chromosomes in the GnomAD database, including 85,863 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10501 hom., cov: 31)
  • Exomes 𝑓: 0.31 (75362 hom.)
• Consequence: OR4S1 NM_001004725.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 19 publications found

Genes affected

OR4S1 (HGNC:14705): (olfactory receptor family 4 subfamily S member 1) 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-1.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4S1	NM_001004725.1	c.870C>T	p.Asn290Asn	synonymous_variant	Exon 1 of 1	ENST00000319988.1	NP_001004725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4S1	ENST00000319988.1	c.870C>T	p.Asn290Asn	synonymous_variant	Exon 1 of 1	6	NM_001004725.1	ENSP00000321447.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54153 AN: 151818 Hom.: 10482 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.373

GnomAD2 exomes AF: 0.329 AC: 82738 AN: 251244 AF XY: 0.339

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.419

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.295

Gnomad OTH exome AF: 0.331

GnomAD4 exome AF: 0.313 AC: 457023 AN: 1460700 Hom.: 75362 Cov.: 36 AF XY: 0.318 AC XY: 231263 AN XY: 726678

African (AFR) AF: 0.511 AC: 17099 AN: 33442

American (AMR) AF: 0.226 AC: 10111 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 9009 AN: 26132

East Asian (EAS) AF: 0.372 AC: 14780 AN: 39694

South Asian (SAS) AF: 0.493 AC: 42520 AN: 86220

European-Finnish (FIN) AF: 0.236 AC: 12620 AN: 53412

Middle Eastern (MID) AF: 0.401 AC: 2310 AN: 5764

European-Non Finnish (NFE) AF: 0.295 AC: 327594 AN: 1110958

Other (OTH) AF: 0.348 AC: 20980 AN: 60356

GnomAD4 genome AF: 0.357 AC: 54221 AN: 151936 Hom.: 10501 Cov.: 31 AF XY: 0.356 AC XY: 26444 AN XY: 74268

African (AFR) AF: 0.497 AC: 20561 AN: 41400

American (AMR) AF: 0.298 AC: 4547 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3472

East Asian (EAS) AF: 0.424 AC: 2188 AN: 5164

South Asian (SAS) AF: 0.493 AC: 2368 AN: 4808

European-Finnish (FIN) AF: 0.218 AC: 2302 AN: 10554

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 20012 AN: 67958

Other (OTH) AF: 0.372 AC: 786 AN: 2112

Alfa AF: 0.325 Hom.: 4739

Bravo AF: 0.363

Asia WGS AF: 0.509 AC: 1771 AN: 3478

EpiCase AF: 0.315

EpiControl AF: 0.322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.14
DANN	Benign	0.43
PhyloP100		-1.4
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs753095; hg19: chr11-48328644; COSMIC: COSV60679003;