6-55759124-TACACACACACAC-TACACACAC

Variant names:

• chr6-55759124-TACAC-T
• rs749127959
• NM_021073.4:c.1105-13_1105-10delGTGT

Variant summary

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

The NM_021073.4(BMP5):​c.1105-13_1105-10delGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 382,778 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 13)
  • Exomes 𝑓: 0.00015 (0 hom.)
  • Failed GnomAD Quality Control
• 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: 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP5	NM_021073.4	MANE Select	c.1105-13_1105-10delGTGT		intron	N/A	NP_066551.1	P22003-1
	BMP5	NM_001329754.2		c.1104+1329_1104+1332delGTGT		intron	N/A	NP_001316683.1	P22003-2
	BMP5	NM_001329756.2		c.1028-3446_1028-3443delGTGT		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.1105-13_1105-10delGTGT		intron	N/A	ENSP00000359866.3	P22003-1
	BMP5	ENST00000901523.1		c.1104+1329_1104+1332delGTGT		intron	N/A	ENSP00000571582.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 54204 Hom.: 0 Cov.: 13

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000149 AC: 57 AN: 382778 Hom.: 0 AF XY: 0.000143 AC XY: 31 AN XY: 216634

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000182 AC: 2 AN: 11010

American (AMR) AF: 0.000113 AC: 4 AN: 35254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12662

East Asian (EAS) AF: 0.000227 AC: 4 AN: 17596

South Asian (SAS) AF: 0.0000854 AC: 5 AN: 58566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25728

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

European-Non Finnish (NFE) AF: 0.000183 AC: 37 AN: 201880

Other (OTH) AF: 0.000222 AC: 4 AN: 18040

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 54204 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 23878

African (AFR) AF: 0.00 AC: 0 AN: 13770

American (AMR) AF: 0.00 AC: 0 AN: 3014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1812

East Asian (EAS) AF: 0.00 AC: 0 AN: 1776

South Asian (SAS) AF: 0.00 AC: 0 AN: 1470

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: 0.00 AC: 0 AN: 30474

Other (OTH) AF: 0.00 AC: 0 AN: 626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs749127959; hg19: chr6-55623922;