1-248449969-A-T

Position:

• chr1-248449969-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001004136.2(OR2T2):​c.-23+577A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000746 in 130,024 control chromosomes in the GnomAD database, including 14 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 0.00075 (14 hom., cov: 28)
• Consequence: OR2T2 NM_001004136.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

OR2T2 (HGNC:14725): (olfactory receptor family 2 subfamily T member 2) 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T2	NM_001004136.2	c.-23+577A>T		intron_variant		ENST00000641925.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T2	ENST00000641925.2	c.-23+577A>T		intron_variant			NM_001004136.2	P1
OR2T2	ENST00000642130.1	c.-22-2807A>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.000746 AC: 97 AN: 129978 Hom.: 14 Cov.: 28

Gnomad AFR AF: 0.00358

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000218

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000746 AC: 97 AN: 130024 Hom.: 14 Cov.: 28 AF XY: 0.000601 AC XY: 38 AN XY: 63226

Gnomad4 AFR AF: 0.00357

Gnomad4 AMR AF: 0.0000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000219

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1770063; hg19: chr1-248613270;