rs1044104

Positions:

• chr6-7881078-A-G

Variant summary

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

The NM_001718.6(BMP6):​c.*735A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,204 control chromosomes in the GnomAD database, including 9,915 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 0.35 (9910 hom., cov: 33)
  • Exomes 𝑓: 0.27 (5 hom.)
• Consequence: BMP6 NM_001718.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP6	NM_001718.6	c.*735A>G		3_prime_UTR_variant	7/7	ENST00000283147.7	NP_001709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7	c.*735A>G		3_prime_UTR_variant	7/7	1	NM_001718.6	ENSP00000283147	P1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52619 AN: 151998 Hom.: 9886 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.273 AC: 24 AN: 88 Hom.: 5 Cov.: 0 AF XY: 0.300 AC XY: 15 AN XY: 50

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.346 AC: 52691 AN: 152116 Hom.: 9910 Cov.: 33 AF XY: 0.349 AC XY: 25975 AN XY: 74372

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.345

Alfa AF: 0.330 Hom.: 2999

Bravo AF: 0.368

Asia WGS AF: 0.469 AC: 1631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.14
DANN	Benign	0.33

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: rs1044104; hg19: chr6-7881311;