6-7727294-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001718.6(BMP6):c.339G>A(p.Gln113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000864 in 1,606,090 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00066 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (6 hom.)
• Consequence: BMP6 NM_001718.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.126

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 6-7727294-G-A is Benign according to our data. Variant chr6-7727294-G-A is described in ClinVar as [Benign]. Clinvar id is 3056089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.126 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP6	NM_001718.6	c.339G>A	p.Gln113=	synonymous_variant	1/7	ENST00000283147.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP6	ENST00000283147.7	c.339G>A	p.Gln113=	synonymous_variant	1/7	1	NM_001718.6	P1

Frequencies

GnomAD3 genomes AF: 0.000664 AC: 101 AN: 152144 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00104 AC: 233 AN: 224520 Hom.: 1 AF XY: 0.00108 AC XY: 135 AN XY: 124640

Gnomad AFR exome AF: 0.000161

Gnomad AMR exome AF: 0.000568

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000337

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000945

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000885 AC: 1287 AN: 1453830 Hom.: 6 Cov.: 32 AF XY: 0.000873 AC XY: 631 AN XY: 722756

Gnomad4 AFR exome AF: 0.000211

Gnomad4 AMR exome AF: 0.000633

Gnomad4 ASJ exome AF: 0.0115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.000178

Gnomad4 NFE exome AF: 0.000768

Gnomad4 OTH exome AF: 0.00152

GnomAD4 genome AF: 0.000663 AC: 101 AN: 152260 Hom.: 1 Cov.: 32 AF XY: 0.000551 AC XY: 41 AN XY: 74446

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00155 Hom.: 0

Bravo AF: 0.000759

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

Mar 12, 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	-0.62
Cadd	Benign	5.6
Dann	Benign	0.92

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: rs200554660; hg19: chr6-7727527;