rs9505298

Positions:

• chr6-7881216-G-A

Variant summary

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

The NM_001718.6(BMP6):​c.*873G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 152,552 control chromosomes in the GnomAD database, including 764 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 0.066 (764 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (0 hom.)
• Consequence: BMP6 NM_001718.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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]

BLOC1S5-TXNDC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP6	NM_001718.6	c.*873G>A		3_prime_UTR_variant	7/7	ENST00000283147.7
BLOC1S5-TXNDC5	NR_037616.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP6	ENST00000283147.7	c.*873G>A		3_prime_UTR_variant	7/7	1	NM_001718.6	P1

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9952 AN: 152038 Hom.: 766 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0441

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.00576

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.00505 AC: 2 AN: 396 Hom.: 0 Cov.: 0 AF XY: 0.00826 AC XY: 2 AN XY: 242

Gnomad4 FIN exome AF: 0.00515

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0655 AC: 9970 AN: 152156 Hom.: 764 Cov.: 33 AF XY: 0.0636 AC XY: 4729 AN XY: 74404

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0441

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00560

Gnomad4 FIN AF: 0.00576

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0549

Alfa AF: 0.0317 Hom.: 204

Bravo AF: 0.0728

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.64

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: rs9505298; hg19: chr6-7881449;