1-247921110-T-C

Position:

• chr1-247921110-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001005522.2(OR2T8):​c.93T>C​(p.Ser31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00077 in 1,604,488 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00044 (2 hom.)
• Consequence: OR2T8 NM_001005522.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -9.25

Genes affected

OR2T8 (HGNC:15020): (olfactory receptor family 2 subfamily T member 8) 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 1-247921110-T-C is Benign according to our data. Variant chr1-247921110-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2640248.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-9.25 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T8	NM_001005522.2	c.93T>C	p.Ser31=	synonymous_variant	2/2	ENST00000641945.2	NP_001005522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T8	ENST00000641945.2	c.93T>C	p.Ser31=	synonymous_variant	2/2		NM_001005522.2	ENSP00000493286	P1

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 592 AN: 150902 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.00289

GnomAD3 exomes AF: 0.000230 AC: 54 AN: 235102 Hom.: 0 AF XY: 0.000141 AC XY: 18 AN XY: 127562

Gnomad AFR exome AF: 0.00145

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000213

Gnomad OTH exome AF: 0.000353

GnomAD4 exome AF: 0.000439 AC: 638 AN: 1453468 Hom.: 2 Cov.: 31 AF XY: 0.000444 AC XY: 321 AN XY: 723214

Gnomad4 AFR exome AF: 0.00484

Gnomad4 AMR exome AF: 0.000715

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000356

Gnomad4 OTH exome AF: 0.000816

GnomAD4 genome AF: 0.00396 AC: 598 AN: 151020 Hom.: 3 Cov.: 31 AF XY: 0.00374 AC XY: 276 AN XY: 73720

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.00125

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00143

Gnomad4 OTH AF: 0.00430

Alfa AF: 0.00350 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

OR2T8: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.8
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs201400439; hg19: chr1-248084412;