X-131619414-A-G

Position:

• chrX-131619414-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000454899.2(OR2AF1P):​n.402A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 110,158 control chromosomes in the GnomAD database, including 5,557 homozygotes. There are 11,361 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 0.36 (5555 hom., 11357 hem., cov: 22)
  • Exomes 𝑓: 0.80 (2 hom. 4 hem.)
• Consequence: OR2AF1P ENST00000454899.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

Genes affected

OR2AF1P (HGNC:14719): (olfactory receptor family 2 subfamily AF member 1 pseudogene) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2AF1P	ENST00000454899.2	n.402A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 39763 AN: 110092 Hom.: 5560 Cov.: 22 AF XY: 0.350 AC XY: 11340 AN XY: 32422

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.476

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.800 AC: 8 AN: 10 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 NFE exome AF: 0.800

GnomAD4 genome AF: 0.361 AC: 39756 AN: 110148 Hom.: 5555 Cov.: 22 AF XY: 0.350 AC XY: 11357 AN XY: 32488

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.350

Alfa AF: 0.419 Hom.: 39408

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.012
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10521771; hg19: chrX-130753416;