Genetic Variant BMP5:c.1105-21_1105-10dupGTGTGTGTGTGT (chr6-55759124-T-TACACACACACAC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_021073.4(BMP5):c.1105-21_1105-10dupGTGTGTGTGTGT 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 0.00050 ( 0 hom., cov: 18)

Exomes 𝑓: 0.00053 ( 13 hom. )

Consequence

BMP5
NM_021073.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.73

Publications

0 publications found

Variant links:

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

BMP5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 13 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BMP5	NM_021073.4	MANE Select	c.1105-21_1105-10dupGTGTGTGTGTGT	intron	N/A	NP_066551.1	P22003-1
BMP5	NM_001329754.2		c.1104+1321_1104+1332dupGTGTGTGTGTGT	intron	N/A	NP_001316683.1	P22003-2
BMP5	NM_001329756.2		c.1028-3454_1028-3443dupGTGTGTGTGTGT	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_1105-9insGTGTGTGTGTGT		intron	N/A	ENSP00000359866.3	P22003-1
	BMP5	ENST00000901523.1		c.1104+1332_1104+1333insGTGTGTGTGTGT		intron	N/A	ENSP00000571582.1

Frequencies

GnomAD3 genomes

AF:

0.000498

AC:

AN:

54204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

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:

0.000788

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000530

AC:

203

AN:

383004

Hom.:

Cov.:

AF XY:

0.000554

AC XY:

120

AN XY:

216752

show subpopulations

African (AFR)

AF:

0.000182

AC:

AN:

11012

American (AMR)

AF:

0.000284

AC:

AN:

35272

Ashkenazi Jewish (ASJ)

AF:

0.0000789

AC:

AN:

12672

East Asian (EAS)

AF:

0.0000567

AC:

AN:

17624

South Asian (SAS)

AF:

0.000529

AC:

AN:

58592

European-Finnish (FIN)

AF:

0.000427

AC:

AN:

25738

Middle Eastern (MID)

AF:

0.000979

AC:

AN:

2042

European-Non Finnish (NFE)

AF:

0.000649

AC:

131

AN:

201996

Other (OTH)

AF:

0.000775

AC:

AN:

18056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.602

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000498

AC:

AN:

54234

Hom.:

Cov.:

AF XY:

0.000502

AC XY:

AN XY:

23898

show subpopulations

African (AFR)

AF:

0.000218

AC:

AN:

13788

American (AMR)

AF:

0.00

AC:

AN:

3018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1812

East Asian (EAS)

AF:

0.00

AC:

AN:

1776

South Asian (SAS)

AF:

0.00

AC:

AN:

1468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000787

AC:

AN:

30478

Other (OTH)

AF:

0.00

AC:

AN:

632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.566

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000119

Hom.:

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

Publications

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6-55759124-TACACACACACAC-TACACACACACACACACACACACAC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over