rs143558290

Variant names:

• chr11-124309928-G-A
• rs143558290
• NM_001002917.2:c.839C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001002917.2(OR8D1):​c.839C>T​(p.Thr280Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000554 in 1,533,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: OR8D1 NM_001002917.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.322
• Publications: 2 publications found

Genes affected

OR8D1 (HGNC:8481): (olfactory receptor family 8 subfamily D member 1) 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0885728).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002917.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8D1	NM_001002917.2	MANE Select	c.839C>T	p.Thr280Met	missense	Exon 3 of 3	NP_001002917.1	A0A126GVG6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8D1	ENST00000641015.1	MANE Select	c.839C>T	p.Thr280Met	missense	Exon 3 of 3	ENSP00000493365.1	Q8WZ84
	OR8D1	ENST00000357821.2	TSL:6	c.839C>T	p.Thr280Met	missense	Exon 1 of 1	ENSP00000350474.2	Q8WZ84
	OR8D1	ENST00000641897.1		c.839C>T	p.Thr280Met	missense	Exon 4 of 4	ENSP00000493091.1	Q8WZ84

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152018 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000323 AC: 6 AN: 185682 AF XY: 0.0000408

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000224

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000507 AC: 70 AN: 1381438 Hom.: 0 Cov.: 30 AF XY: 0.0000574 AC XY: 39 AN XY: 679482

African (AFR) AF: 0.000130 AC: 4 AN: 30658

American (AMR) AF: 0.00 AC: 0 AN: 31186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20446

East Asian (EAS) AF: 0.000384 AC: 15 AN: 39086

South Asian (SAS) AF: 0.000139 AC: 10 AN: 71922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5340

European-Non Finnish (NFE) AF: 0.0000344 AC: 37 AN: 1075774

Other (OTH) AF: 0.0000703 AC: 4 AN: 56864

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74346

African (AFR) AF: 0.000193 AC: 8 AN: 41532

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68006

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000201 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000332 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.99	L
PhyloP100		0.32
PrimateAI	Benign	0.16	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.050
Sift	Uncertain	0.022	D
Sift4G	Benign	0.14	T
Polyphen		0.99	D
Vest4		0.19
MVP		0.26
MPC		0.15
ClinPred		0.052	T
GERP RS		1.3
Varity_R		0.033
gMVP		0.092
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: rs143558290; hg19: chr11-124179824;