6-7727289-G-GAGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.026 (123 hom., cov: 32)
  • Exomes 𝑓: 0.019 (640 hom.)
• Consequence: BMP6 NM_001718.6 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.869

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 -10 ACMG points.

• 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 criteria_provided_single_submitter, 1 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	UniProt
BMP6	NM_001718.6	c.353_355dup	p.Gln118dup	inframe_insertion	1/7	ENST00000283147.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP6	ENST00000283147.7	c.353_355dup	p.Gln118dup	inframe_insertion	1/7	1	NM_001718.6	P1

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4015 AN: 152048 Hom.: 124 Cov.: 32

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

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.: 32 AF XY: 0.0199 AC XY: 14392 AN XY: 722698

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.: 32 AF XY: 0.0291 AC XY: 2167 AN XY: 74378

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: criteria provided, single submitter

Submissions by phenotype

BMP6-related disorder Benign:1

Benign, criteria provided, single submitter

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs537332654; hg19: chr6-7727522;