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. Variant got -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. 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
BMP5	NM_021073.4 link	c.1105-21_1105-10dupGTGTGTGTGTGT	intron_variant	Intron 5 of 6	ENST00000370830.4	NP_066551.1	P22003-1M9VUD0A8K694
BMP5	NM_001329754.2 link	c.1104+1321_1104+1332dupGTGTGTGTGTGT	intron_variant	Intron 5 of 5		NP_001316683.1	P22003-2A8K694
BMP5	NM_001329756.2 link	c.1028-3454_1028-3443dupGTGTGTGTGTGT	intron_variant	Intron 4 of 4		NP_001316685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP5	ENST00000370830.4 link	c.1105-10_1105-9insGTGTGTGTGTGT		intron_variant	Intron 5 of 6	1	NM_021073.4	ENSP00000359866.3		P22003-1

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

Gnomad4 AFR exome

AF:

0.000182

Gnomad4 AMR exome

AF:

0.000284

Gnomad4 ASJ exome

AF:

0.0000789

Gnomad4 EAS exome

AF:

0.0000567

Gnomad4 SAS exome

AF:

0.000529

Gnomad4 FIN exome

AF:

0.000427

Gnomad4 NFE exome

AF:

0.000649

Gnomad4 OTH exome

AF:

0.000775

GnomAD4 genome

AF:

0.000498

AC:

AN:

54234

Hom.:

Cov.:

AF XY:

0.000502

AC XY:

AN XY:

23898

show subpopulations

Gnomad4 AFR

AF:

0.000218

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000787

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over