rs201788022

Variant names:

• chr6-7727180-G-A
• rs201788022
• NM_001718.6:c.225G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_001718.6(BMP6):​c.225G>A​(p.Glu75Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00373 in 1,599,744 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (26 hom.)
• Consequence: BMP6 NM_001718.6 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.48
• Publications: 1 publications found

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]

BMP6 Gene-Disease associations (from GenCC):

• hemochromatosis type 5

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• iron overload, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 6-7727180-G-A is Benign according to our data. Variant chr6-7727180-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056390.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 484 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001718.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	NM_001718.6	MANE Select	c.225G>A	p.Glu75Glu	synonymous	Exon 1 of 7	NP_001709.1	P22004

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	ENST00000283147.7	TSL:1 MANE Select	c.225G>A	p.Glu75Glu	synonymous	Exon 1 of 7	ENSP00000283147.6	P22004
	BMP6	ENST00000946083.1		c.225G>A	p.Glu75Glu	synonymous	Exon 1 of 7	ENSP00000616142.1

Frequencies

GnomAD3 genomes AF: 0.00318 AC: 484 AN: 151974 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00344

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00366 AC: 784 AN: 214444 AF XY: 0.00377

Gnomad AFR exome AF: 0.000515

Gnomad AMR exome AF: 0.00115

Gnomad ASJ exome AF: 0.0122

Gnomad EAS exome AF: 0.0000616

Gnomad FIN exome AF: 0.0107

Gnomad NFE exome AF: 0.00434

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00379 AC: 5488 AN: 1447658 Hom.: 26 Cov.: 32 AF XY: 0.00372 AC XY: 2673 AN XY: 719222

African (AFR) AF: 0.000667 AC: 22 AN: 32964

American (AMR) AF: 0.00141 AC: 61 AN: 43252

Ashkenazi Jewish (ASJ) AF: 0.0119 AC: 305 AN: 25736

East Asian (EAS) AF: 0.00 AC: 0 AN: 38996

South Asian (SAS) AF: 0.000177 AC: 15 AN: 84920

European-Finnish (FIN) AF: 0.0115 AC: 578 AN: 50280

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5692

European-Non Finnish (NFE) AF: 0.00385 AC: 4263 AN: 1106138

Other (OTH) AF: 0.00407 AC: 243 AN: 59680

GnomAD4 genome AF: 0.00318 AC: 484 AN: 152086 Hom.: 2 Cov.: 33 AF XY: 0.00351 AC XY: 261 AN XY: 74354

African (AFR) AF: 0.000794 AC: 33 AN: 41536

American (AMR) AF: 0.00157 AC: 24 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 47 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.0131 AC: 138 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00344 AC: 234 AN: 67950

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00425 Hom.: 3

Bravo AF: 0.00234

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	BMP6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Uncertain	0.98
PhyloP100		4.5
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201788022; hg19: chr6-7727413;