chr6-55759124-T-TACACACAC

Variant names:

• chr6-55759124-T-TACACACAC
• rs749127959
• NM_021073.4:c.1105-17_1105-10dupGTGTGTGT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_021073.4(BMP5):​c.1105-17_1105-10dupGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 18)
  • Exomes 𝑓: 0.0024 (39 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 39 AR gene

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.1105-17_1105-10dupGTGTGTGT		intron	N/A	NP_066551.1	P22003-1
	BMP5	NM_001329754.2		c.1104+1325_1104+1332dupGTGTGTGT		intron	N/A	NP_001316683.1	P22003-2
	BMP5	NM_001329756.2		c.1028-3450_1028-3443dupGTGTGTGT		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_1105-9insGTGTGTGT		intron	N/A	ENSP00000359866.3	P22003-1
	BMP5	ENST00000901523.1		c.1104+1332_1104+1333insGTGTGTGT		intron	N/A	ENSP00000571582.1

Frequencies

GnomAD3 genomes AF: 0.000996 AC: 54 AN: 54200 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00221

Gnomad EAS AF: 0.00225

Gnomad SAS AF: 0.000680

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000788

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000800 AC: 171 AN: 213682 AF XY: 0.000773

Gnomad AFR exome AF: 0.00120

Gnomad AMR exome AF: 0.000657

Gnomad ASJ exome AF: 0.000555

Gnomad EAS exome AF: 0.00140

Gnomad FIN exome AF: 0.000284

Gnomad NFE exome AF: 0.000920

Gnomad OTH exome AF: 0.000767

GnomAD4 exome AF: 0.00241 AC: 921 AN: 382938 Hom.: 39 Cov.: 0 AF XY: 0.00233 AC XY: 504 AN XY: 216712

African (AFR) AF: 0.00145 AC: 16 AN: 11012

American (AMR) AF: 0.00102 AC: 36 AN: 35270

Ashkenazi Jewish (ASJ) AF: 0.00229 AC: 29 AN: 12670

East Asian (EAS) AF: 0.00176 AC: 31 AN: 17622

South Asian (SAS) AF: 0.000853 AC: 50 AN: 58588

European-Finnish (FIN) AF: 0.00303 AC: 78 AN: 25734

Middle Eastern (MID) AF: 0.000490 AC: 1 AN: 2042

European-Non Finnish (NFE) AF: 0.00315 AC: 636 AN: 201946

Other (OTH) AF: 0.00244 AC: 44 AN: 18054

GnomAD4 genome AF: 0.000996 AC: 54 AN: 54230 Hom.: 0 Cov.: 18 AF XY: 0.000753 AC XY: 18 AN XY: 23896

African (AFR) AF: 0.00152 AC: 21 AN: 13786

American (AMR) AF: 0.00 AC: 0 AN: 3018

Ashkenazi Jewish (ASJ) AF: 0.00221 AC: 4 AN: 1812

East Asian (EAS) AF: 0.00225 AC: 4 AN: 1776

South Asian (SAS) AF: 0.000681 AC: 1 AN: 1468

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: 0.000788 AC: 24 AN: 30476

Other (OTH) AF: 0.00 AC: 0 AN: 632

Alfa AF: 0.00131 Hom.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

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;