rs146448571

Variant names:

• chr14-20224128-G-A
• rs146448571
• NM_001004480.1:c.419G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-20224128-G-A
• chr14-20224128-G-T

Variant summary

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

The NM_001004480.1(OR11H6):​c.419G>A​(p.Arg140Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000384 in 1,613,542 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (1 hom.)
• Consequence: OR11H6 NM_001004480.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.86
• Publications: 6 publications found

Genes affected

OR11H6 (HGNC:15349): (olfactory receptor family 11 subfamily H member 6) 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=0.24050483).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004480.1. 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
	OR11H6	NM_001004480.1	MANE Select	c.419G>A	p.Arg140Gln	missense	Exon 1 of 1	NP_001004480.1	Q8NGC7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR11H6	ENST00000315519.3	TSL:6 MANE Select	c.419G>A	p.Arg140Gln	missense	Exon 1 of 1	ENSP00000319071.2	Q8NGC7

Frequencies

GnomAD3 genomes AF: 0.000211 AC: 32 AN: 151980 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000653

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000637 AC: 16 AN: 251346 AF XY: 0.0000662

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461562 Hom.: 1 Cov.: 35 AF XY: 0.0000165 AC XY: 12 AN XY: 727106

African (AFR) AF: 0.000239 AC: 8 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53378

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111748

Other (OTH) AF: 0.0000993 AC: 6 AN: 60394

GnomAD4 genome AF: 0.000211 AC: 32 AN: 151980 Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17 AN XY: 74206

African (AFR) AF: 0.000653 AC: 27 AN: 41360

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.000378 AC: 4 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000146 Hom.: 0

Bravo AF: 0.000125

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

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	0.33
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.24	T
MetaSVM	Uncertain	0.33	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		5.9
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.54
Sift	Benign	0.033	D
Sift4G	Uncertain	0.024	D
Polyphen		0.88	P
Vest4		0.27
MVP		0.86
MPC		0.089
ClinPred		0.52	D
GERP RS		5.0
PromoterAI		-0.00030	Neutral
Varity_R		0.38
gMVP		0.62
Mutation Taster		=93/7	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: rs146448571; hg19: chr14-20692287; COSMIC: COSV59643753;