1-247921102-G-C

Variant names:

• chr1-247921102-G-C
• rs138790336
• NM_001005522.2:c.85G>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.85G>C​(p.Val29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 150,924 control chromosomes in the GnomAD database, including 4 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (4 hom., cov: 30)
  • Exomes 𝑓: 0.00062 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T8 NM_001005522.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0140
• 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=0.00566417).
• BP6: Variant 1-247921102-G-C is Benign according to our data. Variant chr1-247921102-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2640245.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.85G>C	p.Val29Leu	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.85G>C	p.Val29Leu	missense_variant	Exon 2 of 2		NM_001005522.2	ENSP00000493286.1

Frequencies

GnomAD3 genomes AF: 0.00404 AC: 610 AN: 150810 Hom.: 4 Cov.: 30

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00139

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: 0.00146

Gnomad OTH AF: 0.00339

GnomAD2 exomes AF: 0.000506 AC: 122 AN: 241212 AF XY: 0.000375

Gnomad AFR exome AF: 0.00347

Gnomad AMR exome AF: 0.000692

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000374

Gnomad OTH exome AF: 0.000515

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000618 AC: 900 AN: 1456090 Hom.: 2 Cov.: 31 AF XY: 0.000616 AC XY: 446 AN XY: 724434

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

African (AFR) AF: 0.00589 AC: 195 AN: 33094

American (AMR) AF: 0.00116 AC: 51 AN: 43862

Ashkenazi Jewish (ASJ) AF: 0.0000386 AC: 1 AN: 25932

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85874

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.000526 AC: 583 AN: 1108372

Other (OTH) AF: 0.00108 AC: 65 AN: 60180

⚠️ 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: 0.00408 AC: 616 AN: 150924 Hom.: 4 Cov.: 30 AF XY: 0.00380 AC XY: 280 AN XY: 73650

African (AFR) AF: 0.0118 AC: 484 AN: 40994

American (AMR) AF: 0.00138 AC: 21 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5102

South Asian (SAS) AF: 0.000212 AC: 1 AN: 4718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10414

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00146 AC: 99 AN: 67778

Other (OTH) AF: 0.00479 AC: 10 AN: 2086

Alfa AF: 0.000218 Hom.: 0

ExAC AF: 0.000791 AC: 96

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	0.15
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.8
DANN	Benign	0.71
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.24	.;T
MetaRNN	Benign	0.0057	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.20	N;N
PhyloP100		0.014
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.8	.;N
REVEL	Benign	0.016
Sift	Benign	0.072	.;T
Sift4G	Benign	0.11	.;T
Polyphen		0.0010	B;B
Vest4		0.038
MVP		0.21
ClinPred		0.011	T
GERP RS		-3.4
Varity_R		0.14
gMVP		0.098
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs138790336; hg19: chr1-248084404; COSMIC: COSV99082027; COSMIC: COSV99082027;