Variant chr1-39492247-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_181809.4(BMP8A):c.256G>A(p.Gly86Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000553 in 1,559,468 control chromosomes in the GnomAD database, including 11 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00057 ( 10 hom. )

Consequence

BMP8A
NM_181809.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0280

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00521031).

BP6

Variant 1-39492247-G-A is Benign according to our data. Variant chr1-39492247-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024983.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP8A	NM_181809.4 linkuse as main transcript	c.256G>A	p.Gly86Ser	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.256G>A	p.Gly86Ser	missense_variant	1/7	1	NM_181809.4	ENSP00000327440	P1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152034

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:

0.00

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00127

AC:

229

AN:

181028

Hom.:

AF XY:

0.00164

AC XY:

169

AN XY:

103342

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000340

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000830

Gnomad SAS exome

AF:

0.00741

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000304

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000575

AC:

809

AN:

1407326

Hom.:

Cov.:

AF XY:

0.000798

AC XY:

559

AN XY:

700430

show subpopulations

Gnomad4 AFR exome

AF:

0.0000348

Gnomad4 AMR exome

AF:

0.0000247

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00735

Gnomad4 FIN exome

AF:

0.0000548

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.000722

GnomAD4 genome

AF:

0.000348

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00807

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.00112

AC:

124

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

Jan 01, 2024

BMP8A: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.9

DANN

Benign

0.94

DEOGEN2

Benign

0.060

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.12

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.080

REVEL

Benign

0.012

Sift

Benign

0.73

Sift4G

Benign

0.72

Polyphen

0.0070

Vest4

0.10

MutPred

0.36

Gain of phosphorylation at G86 (P = 0.0244);

MVP

0.46

MPC

1.5

ClinPred

0.012

GERP RS

-2.7

Varity_R

0.043

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