NM_021073.4:c.1105-21_1105-10dupGTGTGTGTGTGT

Variant names:

• chr6-55759124-T-TACACACACACAC
• rs749127959
• NM_021073.4:c.1105-21_1105-10dupGTGTGTGTGTGT

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP5	NM_021073.4	c.1105-21_1105-10dupGTGTGTGTGTGT		intron_variant	Intron 5 of 6	ENST00000370830.4	NP_066551.1
BMP5	NM_001329754.2	c.1104+1321_1104+1332dupGTGTGTGTGTGT		intron_variant	Intron 5 of 5		NP_001316683.1
BMP5	NM_001329756.2	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	c.1105-10_1105-9insGTGTGTGTGTGT		intron_variant	Intron 5 of 6	1	NM_021073.4	ENSP00000359866.3

Frequencies

GnomAD3 genomes AF: 0.000498 AC: 27 AN: 54204 Hom.: 0 Cov.: 18

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.: 13 Cov.: 0 AF XY: 0.000554 AC XY: 120 AN XY: 216752

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: 27 AN: 54234 Hom.: 0 Cov.: 18 AF XY: 0.000502 AC XY: 12 AN XY: 23898

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs749127959; hg19: chr6-55623922;