11-123907279-T-C

Variant names:

• chr11-123907279-T-C
• rs7942047
• NM_001005197.2:c.848T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005197.2(OR8D4):​c.848T>C​(p.Leu283Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 1,602,562 control chromosomes in the GnomAD database, including 505,084 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (51510 hom., cov: 31)
  • Exomes 𝑓: 0.79 (453574 hom.)
• Consequence: OR8D4 NM_001005197.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30
• Publications: 26 publications found

Genes affected

OR8D4 (HGNC:14840): (olfactory receptor family 8 subfamily D member 4) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.193187E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8D4	NM_001005197.2	c.848T>C	p.Leu283Pro	missense_variant	Exon 2 of 2	ENST00000641687.1	NP_001005197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR8D4	ENST00000641687.1	c.848T>C	p.Leu283Pro	missense_variant	Exon 2 of 2		NM_001005197.2	ENSP00000493391.1
OR8D4	ENST00000321355.3	c.848T>C	p.Leu283Pro	missense_variant	Exon 1 of 1	6		ENSP00000325381.2

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124800 AN: 151976 Hom.: 51461 Cov.: 31

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.816

GnomAD2 exomes AF: 0.805 AC: 201528 AN: 250194 AF XY: 0.797

Gnomad AFR exome AF: 0.877

Gnomad AMR exome AF: 0.889

Gnomad ASJ exome AF: 0.843

Gnomad EAS exome AF: 0.784

Gnomad FIN exome AF: 0.832

Gnomad NFE exome AF: 0.793

Gnomad OTH exome AF: 0.818

GnomAD4 exome AF: 0.790 AC: 1145503 AN: 1450468 Hom.: 453574 Cov.: 30 AF XY: 0.787 AC XY: 568208 AN XY: 722170

African (AFR) AF: 0.878 AC: 29234 AN: 33292

American (AMR) AF: 0.886 AC: 39517 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 21920 AN: 26050

East Asian (EAS) AF: 0.819 AC: 32398 AN: 39566

South Asian (SAS) AF: 0.699 AC: 60018 AN: 85904

European-Finnish (FIN) AF: 0.831 AC: 44351 AN: 53394

Middle Eastern (MID) AF: 0.824 AC: 4727 AN: 5740

European-Non Finnish (NFE) AF: 0.785 AC: 865324 AN: 1101880

Other (OTH) AF: 0.800 AC: 48014 AN: 60016

GnomAD4 genome AF: 0.821 AC: 124904 AN: 152094 Hom.: 51510 Cov.: 31 AF XY: 0.822 AC XY: 61150 AN XY: 74356

African (AFR) AF: 0.876 AC: 36339 AN: 41476

American (AMR) AF: 0.863 AC: 13191 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2926 AN: 3472

East Asian (EAS) AF: 0.782 AC: 4039 AN: 5166

South Asian (SAS) AF: 0.700 AC: 3362 AN: 4806

European-Finnish (FIN) AF: 0.839 AC: 8886 AN: 10586

Middle Eastern (MID) AF: 0.860 AC: 251 AN: 292

European-Non Finnish (NFE) AF: 0.787 AC: 53491 AN: 67980

Other (OTH) AF: 0.809 AC: 1712 AN: 2116

Alfa AF: 0.801 Hom.: 164117

Bravo AF: 0.829

TwinsUK AF: 0.768 AC: 2849

ALSPAC AF: 0.785 AC: 3026

ESP6500AA AF: 0.874 AC: 3851

ESP6500EA AF: 0.791 AC: 6800

ExAC AF: 0.801 AC: 97256

Asia WGS AF: 0.745 AC: 2588 AN: 3478

EpiCase AF: 0.790

EpiControl AF: 0.792

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.026
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	16
DANN	Benign	0.29
DEOGEN2	Benign	0.0040	T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.066	.;T
MetaRNN	Benign	7.2e-7	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;N
PhyloP100		3.3
PrimateAI	Benign	0.25	T
PROVEAN	Benign	9.4	.;N
REVEL	Benign	0.10
Sift	Benign	1.0	.;T
Sift4G	Benign	1.0	.;T
Polyphen		0.0	B;B
Vest4		0.043
MPC		0.015
ClinPred		0.0026	T
GERP RS		5.7
Varity_R		0.18
gMVP		0.17
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7942047; hg19: chr11-123777986; COSMIC: COSV58430470;