1-39763771-C-T

Position:

chr1-39763771-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001720.5(BMP8B):c.889G>A(p.Gly297Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000532 in 1,600,062 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 32 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 14 hom. )

Consequence

BMP8B
NM_001720.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011675686).

BP6

Variant 1-39763771-C-T is Benign according to our data. Variant chr1-39763771-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638716.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-39763771-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 428 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP8B	NM_001720.5 linkuse as main transcript	c.889G>A	p.Gly297Ser	missense_variant	5/7	ENST00000372827.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP8B	ENST00000372827.8 linkuse as main transcript	c.889G>A	p.Gly297Ser	missense_variant	5/7	1	NM_001720.5	P1	P34820-1
PPIE	ENST00000356511.6 linkuse as main transcript	c.*29C>T		3_prime_UTR_variant	10/10	1			Q9UNP9-2
PPIE	ENST00000372830.5 linkuse as main transcript	c.*110C>T		3_prime_UTR_variant	11/11	1			Q9UNP9-3
PPIE	ENST00000467741.2 linkuse as main transcript	n.483C>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.00288

AC:

429

AN:

149098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00119

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:

0.0000894

Gnomad OTH

AF:

0.000494

GnomAD3 exomes

AF:

0.000670

AC:

167

AN:

249194

Hom.:

AF XY:

0.000527

AC XY:

AN XY:

134746

show subpopulations

Gnomad AFR exome

AF:

0.00822

Gnomad AMR exome

AF:

0.000899

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000292

AC:

423

AN:

1450836

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

175

AN XY:

721696

show subpopulations

Gnomad4 AFR exome

AF:

0.00932

Gnomad4 AMR exome

AF:

0.000875

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000190

Gnomad4 OTH exome

AF:

0.000785

GnomAD4 genome

AF:

0.00287

AC:

428

AN:

149226

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

185

AN XY:

72926

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.00112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000894

Gnomad4 OTH

AF:

0.000488

Alfa

AF:

0.000270

Hom.:

ESP6500AA

AF:

0.00730

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000883

AC:

107

EpiCase

AF:

0.0000549

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

BMP8B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.32

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.67

MetaRNN

Benign

0.012

MetaSVM

Uncertain

-0.086

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

REVEL

Benign

0.22

Sift

Benign

0.50

Sift4G

Benign

0.72

Polyphen

0.93

Vest4

0.23

MVP

0.75

ClinPred

0.014

GERP RS

4.0

Varity_R

0.023

gMVP

0.51

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over