chr11-48489467-C-G

Variant names:

• chr11-48489467-C-G
• rs774349068
• NM_001005512.2:c.675C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005512.2(OR4A47):​c.675C>G​(p.Asn225Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OR4A47 NM_001005512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.28
• Publications: 5 publications found

Genes affected

OR4A47 (HGNC:31266): (olfactory receptor family 4 subfamily A member 47) 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06290913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005512.2. 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
	OR4A47	NM_001005512.2	MANE Select	c.675C>G	p.Asn225Lys	missense	Exon 1 of 1	NP_001005512.2	Q6IF82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4A47	ENST00000446524.2	TSL:6 MANE Select	c.675C>G	p.Asn225Lys	missense	Exon 1 of 1	ENSP00000412752.1	Q6IF82

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461610 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727106

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111824

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.16
DANN	Benign	0.84
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.1	T
PhyloP100		-6.3
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.018
Sift	Benign	0.062	T
Sift4G	Benign	0.16	T
Polyphen		0.019	B
Vest4		0.094
MutPred		0.37		Gain of MoRF binding (P = 0.034)
MVP		0.22
ClinPred		0.042	T
GERP RS		2.7
Varity_R		0.11
gMVP		0.070
Mutation Taster		=97/3	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: rs774349068; hg19: chr11-48511019;