Genetic Variant NM_021073.4:c.1105-21_1105-10delGTGTGTGTGTGT (chr6-55759124-TACACACACACAC-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_021073.4(BMP5):c.1105-21_1105-10delGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 437,226 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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 0.000018 ( 0 hom., cov: 12)

Exomes 𝑓: 0.0000026 ( 0 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: 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

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

Frequencies

GnomAD3 genomes

AF:

0.0000184

AC:

AN:

54204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000328

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000261

AC:

AN:

383022

Hom.:

AF XY:

0.00

AC XY:

AN XY:

216766

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11012

American (AMR)

AF:

0.00

AC:

AN:

35272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12672

East Asian (EAS)

AF:

0.00

AC:

AN:

17624

South Asian (SAS)

AF:

0.00

AC:

AN:

58592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25740

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2042

European-Non Finnish (NFE)

AF:

0.00000495

AC:

AN:

202012

Other (OTH)

AF:

0.00

AC:

AN:

18056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000184

AC:

AN:

54204

Hom.:

Cov.:

AF XY:

0.0000419

AC XY:

AN XY:

23878

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13770

American (AMR)

AF:

0.00

AC:

AN:

3014

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:

1470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000328

AC:

AN:

30474

Other (OTH)

AF:

0.00

AC:

AN:

626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over