rs11964227

Positions:

• chr6-7820436-G-A
• chr6-7820436-G-T

Variant summary

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

The NM_001718.6(BMP6):​c.665-24704G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,106 control chromosomes in the GnomAD database, including 12,504 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 0.40 (12504 hom., cov: 32)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP6	NM_001718.6	c.665-24704G>A		intron_variant		ENST00000283147.7	NP_001709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7	c.665-24704G>A		intron_variant		1	NM_001718.6	ENSP00000283147	P1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60565 AN: 151988 Hom.: 12491 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.399 AC: 60618 AN: 152106 Hom.: 12504 Cov.: 32 AF XY: 0.394 AC XY: 29275 AN XY: 74354

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.389

Alfa AF: 0.357 Hom.: 2115

Bravo AF: 0.393

Asia WGS AF: 0.318 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.78

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: rs11964227; hg19: chr6-7820669;