11-124310747-G-T

Variant names:

• chr11-124310747-G-T
• rs138336307
• NM_001002917.2:c.20C>A

Variant summary

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

The NM_001002917.2(OR8D1):​c.20C>A​(p.Ser7Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 1,610,566 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (25 hom.)
• Consequence: OR8D1 NM_001002917.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.637
• Publications: 9 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004672587).
• BP6: Variant 11-124310747-G-T is Benign according to our data. Variant chr11-124310747-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2642493.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.20C>A	p.Ser7Tyr	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.20C>A	p.Ser7Tyr	missense	Exon 3 of 3	ENSP00000493365.1	Q8WZ84
	OR8D1	ENST00000357821.2	TSL:6	c.20C>A	p.Ser7Tyr	missense	Exon 1 of 1	ENSP00000350474.2	Q8WZ84
	OR8D1	ENST00000641897.1		c.20C>A	p.Ser7Tyr	missense	Exon 4 of 4	ENSP00000493091.1	Q8WZ84

Frequencies

GnomAD3 genomes AF: 0.00359 AC: 546 AN: 152132 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00498

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00455 AC: 1122 AN: 246426 AF XY: 0.00471

Gnomad AFR exome AF: 0.00103

Gnomad AMR exome AF: 0.00115

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.0143

Gnomad NFE exome AF: 0.00605

Gnomad OTH exome AF: 0.00588

GnomAD4 exome AF: 0.00511 AC: 7450 AN: 1458316 Hom.: 25 Cov.: 32 AF XY: 0.00504 AC XY: 3653 AN XY: 725234

African (AFR) AF: 0.000720 AC: 24 AN: 33326

American (AMR) AF: 0.00124 AC: 55 AN: 44280

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25858

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39596

South Asian (SAS) AF: 0.00177 AC: 152 AN: 85996

European-Finnish (FIN) AF: 0.0151 AC: 802 AN: 53286

Middle Eastern (MID) AF: 0.00262 AC: 15 AN: 5718

European-Non Finnish (NFE) AF: 0.00552 AC: 6129 AN: 1110094

Other (OTH) AF: 0.00445 AC: 268 AN: 60162

GnomAD4 genome AF: 0.00359 AC: 546 AN: 152250 Hom.: 3 Cov.: 32 AF XY: 0.00382 AC XY: 284 AN XY: 74436

African (AFR) AF: 0.000890 AC: 37 AN: 41556

American (AMR) AF: 0.000916 AC: 14 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4818

European-Finnish (FIN) AF: 0.0127 AC: 135 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00498 AC: 339 AN: 68012

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00431 Hom.: 4

Bravo AF: 0.00284

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00752 AC: 29

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00396 AC: 34

ExAC AF: 0.00488 AC: 593

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00486

EpiControl AF: 0.00446

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.062
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.64
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.25
MVP		0.71
MPC		0.17
ClinPred		0.059	T
GERP RS		3.5
PromoterAI		0.0058	Neutral
Varity_R		0.21
gMVP		0.19
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: rs138336307; hg19: chr11-124180643; COSMIC: COSV105914140;