chr1-247814867-C-T

Variant names:

• chr1-247814867-C-T
• rs749217143
• NM_001001966.2:c.863G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001001966.2(OR14A16):​c.863G>A​(p.Ser288Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 1,454,950 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (1 hom.)
• Consequence: OR14A16 NM_001001966.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.854
• Publications: 1 publications found

Genes affected

OR14A16 (HGNC:15022): (olfactory receptor family 14 subfamily A member 16) 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34426838).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001966.2. 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
	OR14A16	NM_001001966.2	MANE Select	c.863G>A	p.Ser288Asn	missense	Exon 3 of 3	NP_001001966.1	Q8NHC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR14A16	ENST00000641093.1	MANE Select	c.863G>A	p.Ser288Asn	missense	Exon 3 of 3	ENSP00000493024.1	Q8NHC5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000325 AC: 8 AN: 246078 AF XY: 0.0000150

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: 0.00

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.00000894 AC: 13 AN: 1454950 Hom.: 1 Cov.: 34 AF XY: 0.00000968 AC XY: 7 AN XY: 723228

African (AFR) AF: 0.00 AC: 0 AN: 33128

American (AMR) AF: 0.00 AC: 0 AN: 43536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25818

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.000131 AC: 11 AN: 83904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109822

Other (OTH) AF: 0.0000333 AC: 2 AN: 60078

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000494 AC: 6

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	0.25
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0096	T
Eigen	Benign	0.17
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		0.85
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.63		Gain of MoRF binding (P = 0.1348)
MVP		0.048
MPC		0.45
ClinPred		0.95	D
GERP RS		2.8
Varity_R		0.70
gMVP		0.17
Mutation Taster		=99/1	polymorphism

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: rs749217143; hg19: chr1-247978169;