dbSNP rs140254369: BMP8B:p.Gly297Arg (chr1-39763771-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001720.5(BMP8B):c.889G>C(p.Gly297Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G297S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

BMP8B
NM_001720.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.145

Variant links:

Genes affected

BMP8B (HGNC:1075): (bone morphogenetic protein 8b) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The encoded protein stimulates thermogenesis in brown adipose tissue. Expression of this gene may be downregulated in pancreatic cancer. This gene may have arose from a gene duplication event and its gene duplicate is also present on chromosome 1. [provided by RefSeq, Jul 2016]

BMP8B links:

PPIE (HGNC:9258): (peptidylprolyl isomerase E) The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein contains a highly conserved cyclophilin (CYP) domain as well as an RNA-binding domain. It was shown to possess PPIase and protein folding activities, and it also exhibits RNA-binding activity. Alternative splicing results in multiple transcript variants. A related pseudogene, which is also located on chromosome 1, has been identified. [provided by RefSeq, Aug 2010]

PPIE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34036624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP8B	NM_001720.5 link	c.889G>C	p.Gly297Arg	missense_variant	Exon 5 of 7	ENST00000372827.8	NP_001711.2	P34820-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BMP8B	ENST00000372827.8 link	c.889G>C	p.Gly297Arg	missense_variant	Exon 5 of 7	1	NM_001720.5	ENSP00000361915.3	P34820-1
PPIE	ENST00000372830.5 link	c.*110C>G		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000361918.1	Q9UNP9-3
PPIE	ENST00000356511.6 link	c.*29C>G		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000348904.2	Q9UNP9-2
PPIE	ENST00000467741.2 link	n.483C>G		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149098

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

149098

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72796

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Benign

-0.075

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.69

M_CAP

Benign

0.034

MetaRNN

Benign

0.34

MetaSVM

Uncertain

0.26

MutationAssessor

Benign

2.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.3

REVEL

Benign

0.25

Sift

Benign

0.36

Sift4G

Benign

0.55

Polyphen

0.85

Vest4

0.26

MutPred

0.30

Gain of solvent accessibility (P = 0.0037);

MVP

0.78

ClinPred

0.77

GERP RS

4.0

Varity_R

0.040

gMVP

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over