Variant chr1-39492076-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_181809.4(BMP8A):c.85C>G(p.Pro29Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,130,462 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

BMP8A
NM_181809.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.152

Variant links:

Genes affected

BMP8A (HGNC:21650): (bone morphogenetic protein 8a) 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. This protein may play a role in development of the reproductive system. 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]

BMP8A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03671378).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP8A	NM_181809.4 linkuse as main transcript	c.85C>G	p.Pro29Ala	missense_variant	1/7	ENST00000331593.6	NP_861525.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP8A	ENST00000331593.6 linkuse as main transcript	c.85C>G	p.Pro29Ala	missense_variant	1/7	1	NM_181809.4	ENSP00000327440	P1

Frequencies

GnomAD3 genomes

AF:

0.000134

AC:

AN:

148832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00369

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000203

AC:

199

AN:

981522

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

AN XY:

464118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0123

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000931

Gnomad4 OTH exome

AF:

0.000111

GnomAD4 genome

AF:

0.000134

AC:

AN:

148940

Hom.:

Cov.:

AF XY:

0.0000964

AC XY:

AN XY:

72618

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00370

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000982

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.85C>G (p.P29A) alteration is located in exon 1 (coding exon 1) of the BMP8A gene. This alteration results from a C to G substitution at nucleotide position 85, causing the proline (P) at amino acid position 29 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

4.2

DANN

Benign

0.58

DEOGEN2

Benign

0.084

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.43

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.65

REVEL

Benign

0.10

Sift

Benign

0.56

Sift4G

Benign

0.11

Polyphen

0.0070

Vest4

0.13

MutPred

0.32

Loss of glycosylation at P29 (P = 0.0105);

MVP

0.42

MPC

1.5

ClinPred

0.045

GERP RS

0.71

Varity_R

0.025

gMVP

0.25

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