1-247921109-G-C

Variant names:

• chr1-247921109-G-C
• rs141251148
• NM_001005522.2:c.92G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001005522.2(OR2T8):​c.92G>C​(p.Ser31Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000785 in 1,605,178 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S31G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0040 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00045 (2 hom.)
• Consequence: OR2T8 NM_001005522.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.52
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046643317).
• BP6: Variant 1-247921109-G-C is Benign according to our data. Variant chr1-247921109-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2640247.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T8	NM_001005522.2	c.92G>C	p.Ser31Thr	missense_variant	Exon 2 of 2	ENST00000641945.2	NP_001005522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2T8	ENST00000641945.2	c.92G>C	p.Ser31Thr	missense_variant	Exon 2 of 2		NM_001005522.2	ENSP00000493286.1

Frequencies

GnomAD3 genomes AF: 0.00395 AC: 595 AN: 150728 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00142

Gnomad OTH AF: 0.00290

GnomAD2 exomes AF: 0.000243 AC: 57 AN: 235024 AF XY: 0.000157

Gnomad AFR exome AF: 0.00157

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000223

Gnomad OTH exome AF: 0.000353

GnomAD4 exome AF: 0.000453 AC: 659 AN: 1454334 Hom.: 2 Cov.: 31 AF XY: 0.000459 AC XY: 332 AN XY: 723602

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00492 AC: 163 AN: 33098

American (AMR) AF: 0.000714 AC: 31 AN: 43396

Ashkenazi Jewish (ASJ) AF: 0.0000386 AC: 1 AN: 25892

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.000370 AC: 410 AN: 1107502

Other (OTH) AF: 0.000849 AC: 51 AN: 60102

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00398 AC: 601 AN: 150844 Hom.: 4 Cov.: 31 AF XY: 0.00375 AC XY: 276 AN XY: 73572

African (AFR) AF: 0.0116 AC: 474 AN: 40944

American (AMR) AF: 0.00132 AC: 20 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

South Asian (SAS) AF: 0.000213 AC: 1 AN: 4700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10430

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00142 AC: 96 AN: 67750

Other (OTH) AF: 0.00430 AC: 9 AN: 2092

Alfa AF: 0.00346 Hom.: 1

ExAC AF: 0.000288 AC: 35

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OR2T8: PP2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0040
DANN	Benign	0.39
DEOGEN2	Benign	0.0046	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.054	.;T
MetaRNN	Benign	0.0047	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.095	N;N
PhyloP100		-2.5
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.45	.;N
REVEL	Benign	0.0060
Sift	Benign	0.51	.;T
Sift4G	Benign	0.22	.;T
Polyphen		0.0	B;B
Vest4		0.098
MVP		0.30
ClinPred		0.0082	T
GERP RS		-6.8
Varity_R		0.063
gMVP		0.046
Mutation Taster		=100/0	polymorphism

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: rs141251148; hg19: chr1-248084411;