Variant 6-7727289-G-GAGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM1BP6BA1

The NM_001718.6(BMP6):c.353_355dup(p.Gln118dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,605,868 control chromosomes in the GnomAD database, including 763 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.026 ( 123 hom., cov: 32)

Exomes 𝑓: 0.019 ( 640 hom. )

Consequence

BMP6
NM_001718.6 inframe_insertion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.869

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 -7 ACMG points.

PM1

In a region_of_interest Disordered (size 42) in uniprot entity BMP6_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_001718.6

BP6

Variant 6-7727289-G-GAGC is Benign according to our data. Variant chr6-7727289-G-GAGC is described in ClinVar as [Benign]. Clinvar id is 3037636.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 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.353_355dup	p.Gln118dup	inframe_insertion	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.353_355dup	p.Gln118dup	inframe_insertion	1/7	1	NM_001718.6	ENSP00000283147	P1

Frequencies

GnomAD3 genomes

AF:

0.0264

AC:

4015

AN:

152048

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.0593

Gnomad FIN

AF:

0.0485

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0365

AC:

7569

AN:

207432

Hom.:

217

AF XY:

0.0358

AC XY:

4126

AN XY:

115132

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.0338

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.174

Gnomad SAS exome

AF:

0.0525

Gnomad FIN exome

AF:

0.0456

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.0267

GnomAD4 exome

AF:

0.0189

AC:

27480

AN:

1453704

Hom.:

640

Cov.:

AF XY:

0.0199

AC XY:

14392

AN XY:

722698

show subpopulations

Gnomad4 AFR exome

AF:

0.0307

Gnomad4 AMR exome

AF:

0.0296

Gnomad4 ASJ exome

AF:

0.0127

Gnomad4 EAS exome

AF:

0.148

Gnomad4 SAS exome

AF:

0.0515

Gnomad4 FIN exome

AF:

0.0410

Gnomad4 NFE exome

AF:

0.00980

Gnomad4 OTH exome

AF:

0.0257

GnomAD4 genome

AF:

0.0264

AC:

4024

AN:

152164

Hom.:

123

Cov.:

AF XY:

0.0291

AC XY:

2167

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0298

Gnomad4 AMR

AF:

0.0212

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.164

Gnomad4 SAS

AF:

0.0593

Gnomad4 FIN

AF:

0.0485

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.0246

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

Dec 24, 2019

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

Splicing

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