11-124029632-G-A

Variant names:

• chr11-124029632-G-A
• rs781320865
• NM_001004464.2:c.10G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001004464.2(OR10G8):​c.10G>A​(p.Ala4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: OR10G8 NM_001004464.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.50
• Publications: 2 publications found

Genes affected

OR10G8 (HGNC:14845): (olfactory receptor family 10 subfamily G 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016896129).
• BP6: Variant 11-124029632-G-A is Benign according to our data. Variant chr11-124029632-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2230294.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004464.2. 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
	OR10G8	NM_001004464.2	MANE Select	c.10G>A	p.Ala4Thr	missense	Exon 2 of 2	NP_001004464.1	Q8NGN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10G8	ENST00000641224.2	MANE Select	c.10G>A	p.Ala4Thr	missense	Exon 2 of 2	ENSP00000493087.1	Q8NGN5
	OR10G8	ENST00000431524.1	TSL:6	c.10G>A	p.Ala4Thr	missense	Exon 1 of 1	ENSP00000389072.1	Q8NGN5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000639 AC: 16 AN: 250380 AF XY: 0.0000961

Gnomad AFR exome AF: 0.00

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: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461084 Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21 AN XY: 726746

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111378

Other (OTH) AF: 0.0000828 AC: 5 AN: 60360

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000576 AC: 7

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.072
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0060
DANN	Benign	0.41
DEOGEN2	Benign	0.00093	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.00087	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.84	N
PhyloP100		-4.5
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.0080
Sift	Benign	0.52	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.032
MutPred		0.23		Gain of glycosylation at A4 (P = 0.0466)
MVP		0.15
MPC		0.039
ClinPred		0.028	T
GERP RS		-5.9
PromoterAI		-0.0061	Neutral
Varity_R		0.020
gMVP		0.054
Mutation Taster		=98/2	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: rs781320865; hg19: chr11-123900339;