Variant 6-7727038-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001718.6(BMP6):c.83G>A(p.Arg28Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,134,860 control chromosomes in the GnomAD database, including 117,458 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.37 ( 10975 hom., cov: 33)

Exomes 𝑓: 0.46 ( 106483 hom. )

Consequence

BMP6
NM_001718.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0780

Variant links:

Genes affected

BMP6 (HGNC:1073): (bone morphogenetic protein 6) 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 regulates a wide range of biological processes including iron homeostasis, fat and bone development, and ovulation. Differential expression of this gene may be associated with progression of breast and prostate cancer. Mutations in this gene may be associated with iron overload in human patients. [provided by RefSeq, Jul 2016]

BMP6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.26759205E-5).

BP6

Variant 6-7727038-G-A is Benign according to our data. Variant chr6-7727038-G-A is described in ClinVar as [Benign]. Clinvar id is 3058879.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-7727038-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP6	NM_001718.6 linkuse as main transcript	c.83G>A	p.Arg28Gln	missense_variant	1/7	ENST00000283147.7	NP_001709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7 linkuse as main transcript	c.83G>A	p.Arg28Gln	missense_variant	1/7	1	NM_001718.6	ENSP00000283147	P1

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

54797

AN:

148784

Hom.:

10973

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.441

Gnomad MID

AF:

0.359

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.598

AC:

360

AN:

602

Hom.:

105

AF XY:

0.621

AC XY:

174

AN XY:

280

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad FIN exome

AF:

0.616

Gnomad NFE exome

AF:

0.562

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

AF:

0.462

AC:

455249

AN:

985968

Hom.:

106483

Cov.:

AF XY:

0.462

AC XY:

214761

AN XY:

464384

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.344

Gnomad4 ASJ exome

AF:

0.419

Gnomad4 EAS exome

AF:

0.228

Gnomad4 SAS exome

AF:

0.541

Gnomad4 FIN exome

AF:

0.480

Gnomad4 NFE exome

AF:

0.471

Gnomad4 OTH exome

AF:

0.442

GnomAD4 genome

AF:

0.368

AC:

54819

AN:

148892

Hom.:

10975

Cov.:

AF XY:

0.365

AC XY:

26512

AN XY:

72606

show subpopulations

Gnomad4 AFR

AF:

0.223

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.399

Gnomad4 EAS

AF:

0.230

Gnomad4 SAS

AF:

0.528

Gnomad4 FIN

AF:

0.441

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.347

Alfa

AF:

0.276

Hom.:

712

Bravo

AF:

0.347

TwinsUK

AF:

0.462

AC:

1713

ALSPAC

AF:

0.464

AC:

1787

ExAC

AF:

0.238

AC:

166

Asia WGS

AF:

0.343

AC:

1056

AN:

3080

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BMP6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.57

MetaRNN

Benign

0.000013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.29

REVEL

Benign

0.061

Sift

Benign

0.36

Sift4G

Benign

0.34

Polyphen

0.021

Vest4

0.096

MPC

0.18

ClinPred

0.017

GERP RS

-1.7

Varity_R

0.027

gMVP

0.33

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