NM_014581.4:c.374T>C

Variant names:

• chr9-133207240-A-G
• NM_014581.4:c.374T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014581.4(OBP2B):​c.374T>C​(p.Met125Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,324 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OBP2B NM_014581.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.967
• Publications: 0 publications found

Genes affected

OBP2B (HGNC:23381): (odorant binding protein 2B) Predicted to enable small molecule binding activity. Predicted to be involved in chemosensory behavior. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014581.4. 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
	OBP2B	NM_014581.4	MANE Select	c.374T>C	p.Met125Thr	missense	Exon 4 of 7	NP_055396.1	Q9NPH6-1
	OBP2B	NM_001288987.2		c.374T>C	p.Met125Thr	missense	Exon 4 of 7	NP_001275916.1	Q9NPH6-1
	OBP2B	NR_110242.2		n.531T>C		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBP2B	ENST00000372034.8	TSL:1 MANE Select	c.374T>C	p.Met125Thr	missense	Exon 4 of 7	ENSP00000361104.3	Q9NPH6-1
	OBP2B	ENST00000618116.4	TSL:1	c.374T>C	p.Met125Thr	missense	Exon 4 of 7	ENSP00000484615.1	Q9NPH6-1
	OBP2B	ENST00000461961.2	TSL:1	n.282T>C		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460324 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726582

African (AFR) AF: 0.00 AC: 0 AN: 33446

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110682

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 31

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	0.22
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.3
DANN	Benign	0.37
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0014	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.97
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.17
Sift	Benign	0.045	D
Sift4G	Benign	0.25	T
Polyphen		0.24	B
Vest4		0.28
MutPred		0.83		Loss of stability (P = 0.0343)
MVP		0.040
MPC		0.20
ClinPred		0.14	T
GERP RS		1.9
Varity_R		0.15
gMVP		0.60
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

hg19: chr9-136082627;