6-7727180-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001718.6(BMP6):c.225G>A(p.Glu75=) 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (26 hom.)
• Consequence: BMP6 NM_001718.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.48

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]

ACMG classification

Verdict is Benign. Variant got -8 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 criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP6	NM_001718.6	c.225G>A	p.Glu75=	synonymous_variant	1/7	ENST00000283147.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP6	ENST00000283147.7	c.225G>A	p.Glu75=	synonymous_variant	1/7	1	NM_001718.6	P1

Frequencies

GnomAD3 genomes AF: 0.00318 AC: 484 AN: 151974 Hom.: 2 Cov.: 33

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.: 5 AF XY: 0.00377 AC XY: 447 AN XY: 118674

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.: 26 Cov.: 32 AF XY: 0.00372 AC XY: 2673 AN XY: 719222

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.: 2 Cov.: 33 AF XY: 0.00351 AC XY: 261 AN XY: 74354

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.: 3

Bravo AF: 0.00234

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

BMP6-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 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
BayesDel_noAF	Benign	-0.31
Cadd	Benign	13
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

Other links and lift over

dbSNP: rs201788022; hg19: chr6-7727413;