Variant 6-55759124-T-TAC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_021073.4(BMP5):c.1105-10_1105-9insGT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.025 ( 66 hom., cov: 18)

Exomes 𝑓: 0.024 ( 202 hom. )

Consequence

BMP5
NM_021073.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

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 Benign. Variant got -9 ACMG points.

BP6

Variant 6-55759124-T-TAC is Benign according to our data. Variant chr6-55759124-T-TAC is described in ClinVar as [Likely_benign]. Clinvar id is 3060530.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0248 (1344/54212) while in subpopulation NFE AF= 0.0265 (809/30472). AF 95% confidence interval is 0.025. There are 66 homozygotes in gnomad4. There are 595 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1344 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
BMP5	NM_021073.4 linkuse as main transcript	c.1105-10_1105-9insGT	splice_polypyrimidine_tract_variant, intron_variant	ENST00000370830.4	NP_066551.1
BMP5	NM_001329754.2 linkuse as main transcript	c.1104+1332_1104+1333insGT	intron_variant		NP_001316683.1
BMP5	NM_001329756.2 linkuse as main transcript	c.1028-3443_1028-3442insGT	intron_variant		NP_001316685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP5	ENST00000370830.4 linkuse as main transcript	c.1105-10_1105-9insGT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_021073.4	ENSP00000359866	P1	P22003-1

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

1343

AN:

54182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.0129

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.0293

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.0136

Gnomad FIN

AF:

0.00917

Gnomad MID

AF:

0.0606

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0288

GnomAD3 exomes

AF:

0.0113

AC:

2407

AN:

213682

Hom.:

AF XY:

0.0117

AC XY:

1366

AN XY:

116414

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.00927

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.00887

Gnomad SAS exome

AF:

0.0153

Gnomad FIN exome

AF:

0.00681

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0240

AC:

9172

AN:

381964

Hom.:

202

Cov.:

AF XY:

0.0244

AC XY:

5275

AN XY:

216182

show subpopulations

Gnomad4 AFR exome

AF:

0.0246

Gnomad4 AMR exome

AF:

0.00968

Gnomad4 ASJ exome

AF:

0.0253

Gnomad4 EAS exome

AF:

0.0184

Gnomad4 SAS exome

AF:

0.0197

Gnomad4 FIN exome

AF:

0.0200

Gnomad4 NFE exome

AF:

0.0283

Gnomad4 OTH exome

AF:

0.0273

GnomAD4 genome

AF:

0.0248

AC:

1344

AN:

54212

Hom.:

Cov.:

AF XY:

0.0249

AC XY:

595

AN XY:

23888

show subpopulations

Gnomad4 AFR

AF:

0.0258

Gnomad4 AMR

AF:

0.0156

Gnomad4 ASJ

AF:

0.0293

Gnomad4 EAS

AF:

0.0135

Gnomad4 SAS

AF:

0.0136

Gnomad4 FIN

AF:

0.00917

Gnomad4 NFE

AF:

0.0265

Gnomad4 OTH

AF:

0.0285

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BMP5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 27, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over