Genetic Variant BMP6:c.665-129C>T (chr6-7845011-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001718.6(BMP6):c.665-129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 801,822 control chromosomes in the GnomAD database, including 68,673 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 11896 hom., cov: 32)

Exomes 𝑓: 0.41 ( 56777 hom. )

Consequence

BMP6
NM_001718.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

hemochromatosis type 5
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

BMP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6 link	c.665-129C>T		intron_variant	Intron 1 of 6	ENST00000283147.7	NP_001709.1	P22004Q4VBA3B4DUF7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7 link	c.665-129C>T		intron_variant	Intron 1 of 6	1	NM_001718.6	ENSP00000283147.6		P22004

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58354

AN:

151882

Hom.:

11888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.714

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.383

GnomAD4 exome

AF:

0.405

AC:

263227

AN:

649822

Hom.:

56777

AF XY:

0.402

AC XY:

135629

AN XY:

337410

show subpopulations

African (AFR)

AF:

0.318

AC:

5250

AN:

16488

American (AMR)

AF:

0.591

AC:

15007

AN:

25392

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

3991

AN:

15204

East Asian (EAS)

AF:

0.747

AC:

25993

AN:

34814

South Asian (SAS)

AF:

0.394

AC:

20114

AN:

51020

European-Finnish (FIN)

AF:

0.424

AC:

18546

AN:

43748

Middle Eastern (MID)

AF:

0.317

AC:

727

AN:

2290

European-Non Finnish (NFE)

AF:

0.376

AC:

160787

AN:

428084

Other (OTH)

AF:

0.391

AC:

12812

AN:

32782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

7227

14454

21681

28908

36135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3080

6160

9240

12320

15400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.384

AC:

58399

AN:

152000

Hom.:

11896

Cov.:

AF XY:

0.391

AC XY:

29077

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.320

AC:

13262

AN:

41448

American (AMR)

AF:

0.486

AC:

7428

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

870

AN:

3468

East Asian (EAS)

AF:

0.715

AC:

3681

AN:

5150

South Asian (SAS)

AF:

0.397

AC:

1912

AN:

4816

European-Finnish (FIN)

AF:

0.421

AC:

4441

AN:

10550

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.373

AC:

25357

AN:

67958

Other (OTH)

AF:

0.388

AC:

820

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1757

3514

5270

7027

8784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.243

Hom.:

575

Bravo

AF:

0.392

Asia WGS

AF:

0.564

AC:

1961

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.86

(source)

DANN

Benign

0.78

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over