rs270406

chr6-7737575-A-Gchr6-7737575-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001718.6(BMP6):c.664+9956A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,864 control chromosomes in the GnomAD database, including 27,541 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 0.60 (27541 hom., cov: 31)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP6	NM_001718.6	c.664+9956A>G		intron_variant		ENST00000283147.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP6	ENST00000283147.7	c.664+9956A>G		intron_variant		1	NM_001718.6	P1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91105 AN: 151758 Hom.: 27510 Cov.: 31

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.585

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.600 AC: 91189 AN: 151864 Hom.: 27541 Cov.: 31 AF XY: 0.603 AC XY: 44760 AN XY: 74208

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.582

Alfa AF: 0.563 Hom.: 33610

Bravo AF: 0.593

Asia WGS AF: 0.659 AC: 2291 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.18
Dann	Benign	0.44

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: rs270406; hg19: chr6-7737808;