chr9-133205932-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OBP2B	NM_014581.4	c.499G>A	p.Val167Ile	missense_variant	Exon 6 of 7	ENST00000372034.8	NP_055396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OBP2B	ENST00000372034.8	c.499G>A	p.Val167Ile	missense_variant	Exon 6 of 7	1	NM_014581.4	ENSP00000361104.3

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

GnomAD3 exomes AF: 0.0785 AC: 19703 AN: 250984 Hom.: 581 AF XY: 0.0793 AC XY: 10757 AN XY: 135648

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 SAS exome AF: 0.0350

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

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.0673

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0213

Gnomad4 FIN exome AF: 0.0748

Gnomad4 NFE exome AF: 0.0409

Gnomad4 OTH exome AF: 0.0475

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

Gnomad4 AFR AF: 0.0258

Gnomad4 AMR AF: 0.0708

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.000775

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.0951

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0808

Alfa AF: 0.0901 Hom.: 351

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 v4.3

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;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;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.17	N;.
REVEL	Benign	0.0020
Sift	Benign	0.31	T;.
Sift4G	Benign	0.29	T;T
Polyphen		0.12	B;B
Vest4		0.047
MPC		0.14
ClinPred		0.00045	T
GERP RS		-3.3
Varity_R		0.015
gMVP		0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs11244035; hg19: chr9-136081319;