rs17316625

Positions:

• chrX-131544622-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001004486.1(OR13H1):​c.549C>G​(p.Leu183=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,207,438 control chromosomes in the GnomAD database, including 46,625 homozygotes. There are 130,590 hemizygotes in GnomAD. 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 0.24 (3072 hom., 7884 hem., cov: 22)
  • Exomes 𝑓: 0.34 (43553 hom. 122706 hem.)
• Consequence: OR13H1 NM_001004486.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

Genes affected

OR13H1 (HGNC:14755): (olfactory receptor family 13 subfamily H 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]

IGSF1 (HGNC:5948): (immunoglobulin superfamily member 1) This gene encodes a member of the immunoglobulin-like domain-containing superfamily. Proteins in this superfamily contain varying numbers of immunoglobulin-like domains and are thought to participate in the regulation of interactions between cells. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-2.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR13H1	NM_001004486.1	c.549C>G	p.Leu183=	synonymous_variant	1/1	ENST00000338616.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR13H1	ENST00000338616.6	c.549C>G	p.Leu183=	synonymous_variant	1/1		NM_001004486.1	P1
IGSF1	ENST00000370904.6	c.-913+34046G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 26935 AN: 110974 Hom.: 3074 Cov.: 22 AF XY: 0.237 AC XY: 7877 AN XY: 33190

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0428

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.254

GnomAD3 exomes AF: 0.277 AC: 50511 AN: 182641 Hom.: 4969 AF XY: 0.298 AC XY: 20011 AN XY: 67237

Gnomad AFR exome AF: 0.0456

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.354

Gnomad EAS exome AF: 0.0440

Gnomad SAS exome AF: 0.346

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.353

Gnomad OTH exome AF: 0.300

GnomAD4 exome AF: 0.336 AC: 368274 AN: 1096415 Hom.: 43553 Cov.: 34 AF XY: 0.339 AC XY: 122706 AN XY: 362007

Gnomad4 AFR exome AF: 0.0433

Gnomad4 AMR exome AF: 0.170

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.0527

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.334

Gnomad4 NFE exome AF: 0.362

Gnomad4 OTH exome AF: 0.311

GnomAD4 genome AF: 0.243 AC: 26930 AN: 111023 Hom.: 3072 Cov.: 22 AF XY: 0.237 AC XY: 7884 AN XY: 33249

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.0432

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.255

Alfa AF: 0.300 Hom.: 2909

Bravo AF: 0.226

EpiCase AF: 0.375

EpiControl AF: 0.376

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.58

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: rs17316625; hg19: chrX-130678596; COSMIC: COSV58547028;