9-133205932-C-T

Variant names:

• chr9-133205932-C-T
• rs11244035
• NM_014581.4:c.499G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014581.4(OBP2B):​c.499G>A​(p.Val167Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 1,445,958 control chromosomes in the GnomAD database, including 2,507 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.073 (461 hom., cov: 35)
  • Exomes 𝑓: 0.040 (2046 hom.)
• Consequence: OBP2B NM_014581.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018077791).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBP2B	NM_014581.4	MANE Select	c.499G>A	p.Val167Ile	missense	Exon 6 of 7	NP_055396.1
	OBP2B	NM_001288987.2		c.499G>A	p.Val167Ile	missense	Exon 6 of 7	NP_001275916.1
	OBP2B	NR_110242.2		n.656G>A		non_coding_transcript_exon	Exon 7 of 8

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBP2B	ENST00000372034.8	TSL:1 MANE Select	c.499G>A	p.Val167Ile	missense	Exon 6 of 7	ENSP00000361104.3
	OBP2B	ENST00000618116.4	TSL:1	c.499G>A	p.Val167Ile	missense	Exon 6 of 7	ENSP00000484615.1
	OBP2B	ENST00000461961.2	TSL:1	n.407G>A		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11028 AN: 151048 Hom.: 461 Cov.: 35

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.0709

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0951

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0816

GnomAD2 exomes AF: 0.0785 AC: 19703 AN: 250984 AF XY: 0.0793

Gnomad AFR exome AF: 0.0231

Gnomad AMR exome AF: 0.0629

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.0949

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.0890

GnomAD4 exome AF: 0.0397 AC: 51410 AN: 1294790 Hom.: 2046 Cov.: 44 AF XY: 0.0406 AC XY: 26238 AN XY: 646832

African (AFR) AF: 0.0112 AC: 366 AN: 32626

American (AMR) AF: 0.0385 AC: 1619 AN: 42040

Ashkenazi Jewish (ASJ) AF: 0.0673 AC: 1607 AN: 23876

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.0213 AC: 1782 AN: 83532

European-Finnish (FIN) AF: 0.0748 AC: 3852 AN: 51472

Middle Eastern (MID) AF: 0.0522 AC: 278 AN: 5330

European-Non Finnish (NFE) AF: 0.0409 AC: 39271 AN: 960814

Other (OTH) AF: 0.0475 AC: 2634 AN: 55414

GnomAD4 genome AF: 0.0729 AC: 11019 AN: 151168 Hom.: 461 Cov.: 35 AF XY: 0.0709 AC XY: 5241 AN XY: 73882

African (AFR) AF: 0.0258 AC: 1069 AN: 41406

American (AMR) AF: 0.0708 AC: 1076 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 365 AN: 3444

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5160

South Asian (SAS) AF: 0.0311 AC: 149 AN: 4786

European-Finnish (FIN) AF: 0.0951 AC: 998 AN: 10498

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.102 AC: 6898 AN: 67400

Other (OTH) AF: 0.0808 AC: 169 AN: 2092

Alfa AF: 0.0868 Hom.: 552

TwinsUK AF: 0.0995 AC: 369

ALSPAC AF: 0.0919 AC: 354

ESP6500AA AF: 0.0277 AC: 122

ESP6500EA AF: 0.103 AC: 883

ExAC AF: 0.0796 AC: 9659

Asia WGS AF: 0.00872 AC: 30 AN: 3454

EpiCase AF: 0.108

EpiControl AF: 0.108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.14
DANN	Benign	0.58
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-2.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.0020
Sift	Benign	0.31	T
Sift4G	Benign	0.29	T
Polyphen		0.12	B
Vest4		0.047
MPC		0.14
ClinPred		0.00045	T
GERP RS		-3.3
Varity_R		0.015
gMVP		0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs11244035; hg19: chr9-136081319; COSMIC: COSV107460002;