Genetic Variant NM_001718.6:c.225G>A (chr6-7727180-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001718.6(BMP6):c.225G>A(p.Glu75Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00373 in 1,599,744 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 26 hom. )

Consequence

BMP6
NM_001718.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.48

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.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 6-7727180-G-A is Benign according to our data. Variant chr6-7727180-G-A is described in ClinVar as [Benign]. Clinvar id is 3056390.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6 link	c.225G>A	p.Glu75Glu	synonymous_variant	Exon 1 of 7	ENST00000283147.7	NP_001709.1	P22004Q4VBA3B4DUF7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7 link	c.225G>A	p.Glu75Glu	synonymous_variant	Exon 1 of 7	1	NM_001718.6	ENSP00000283147.6		P22004

Frequencies

GnomAD3 genomes

AF:

0.00318

AC:

484

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0131

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00344

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00366

AC:

784

AN:

214444

Hom.:

AF XY:

0.00377

AC XY:

447

AN XY:

118674

show subpopulations

Gnomad AFR exome

AF:

0.000515

Gnomad AMR exome

AF:

0.00115

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.0000616

Gnomad SAS exome

AF:

0.000208

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.00434

Gnomad OTH exome

AF:

0.00394

GnomAD4 exome

AF:

0.00379

AC:

5488

AN:

1447658

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

2673

AN XY:

719222

show subpopulations

Gnomad4 AFR exome

AF:

0.000667

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000177

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.00385

Gnomad4 OTH exome

AF:

0.00407

GnomAD4 genome

AF:

0.00318

AC:

484

AN:

152086

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

261

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.0136

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0131

Gnomad4 NFE

AF:

0.00344

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00425

Hom.:

Bravo

AF:

0.00234

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BMP6-related disorder

Benign:1

Feb 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.98

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