6-55759124-TACACACACACAC-TACACACACACACACACACACACACAC

Variant names:

• chr6-55759124-T-TACACACACACACAC
• rs749127959
• NM_021073.4:c.1105-23_1105-10dupGTGTGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_021073.4(BMP5):​c.1105-23_1105-10dupGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000074 (1 hom., cov: 18)
  • Exomes 𝑓: 0.000044 (1 hom.)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 0 publications found

Genes affected

BMP5 (HGNC:1072): (bone morphogenetic protein 5) 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, which plays a role in bone and cartilage development. Polymorphisms in this gene may be associated with osteoarthritis in human patients. This gene is differentially regulated in multiple human cancers. This gene encodes distinct protein isoforms that may be similarly proteolytically processed. [provided by RefSeq, Jul 2016]

BMP5 Gene-Disease associations (from GenCC):

• dysostosis

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021073.4. 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
	BMP5	NM_021073.4	MANE Select	c.1105-23_1105-10dupGTGTGTGTGTGTGT		intron	N/A	NP_066551.1	P22003-1
	BMP5	NM_001329754.2		c.1104+1319_1104+1332dupGTGTGTGTGTGTGT		intron	N/A	NP_001316683.1	P22003-2
	BMP5	NM_001329756.2		c.1028-3456_1028-3443dupGTGTGTGTGTGTGT		intron	N/A	NP_001316685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP5	ENST00000370830.4	TSL:1 MANE Select	c.1105-10_1105-9insGTGTGTGTGTGTGT		intron	N/A	ENSP00000359866.3	P22003-1
	BMP5	ENST00000901523.1		c.1104+1332_1104+1333insGTGTGTGTGTGTGT		intron	N/A	ENSP00000571582.1

Frequencies

GnomAD3 genomes AF: 0.0000738 AC: 4 AN: 54204 Hom.: 1 Cov.: 18

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000984

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000444 AC: 17 AN: 383022 Hom.: 1 Cov.: 0 AF XY: 0.0000369 AC XY: 8 AN XY: 216766

African (AFR) AF: 0.000182 AC: 2 AN: 11012

American (AMR) AF: 0.0000284 AC: 1 AN: 35272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12672

East Asian (EAS) AF: 0.00 AC: 0 AN: 17624

South Asian (SAS) AF: 0.0000171 AC: 1 AN: 58592

European-Finnish (FIN) AF: 0.0000389 AC: 1 AN: 25740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2042

European-Non Finnish (NFE) AF: 0.0000545 AC: 11 AN: 202012

Other (OTH) AF: 0.0000554 AC: 1 AN: 18056

GnomAD4 genome AF: 0.0000738 AC: 4 AN: 54204 Hom.: 1 Cov.: 18 AF XY: 0.000168 AC XY: 4 AN XY: 23878

African (AFR) AF: 0.0000726 AC: 1 AN: 13770

American (AMR) AF: 0.00 AC: 0 AN: 3014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1812

East Asian (EAS) AF: 0.00 AC: 0 AN: 1776

South Asian (SAS) AF: 0.00 AC: 0 AN: 1470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 66

European-Non Finnish (NFE) AF: 0.0000984 AC: 3 AN: 30474

Other (OTH) AF: 0.00 AC: 0 AN: 626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs749127959; hg19: chr6-55623922;