NM_021073.4:c.1105-17_1105-10dupGTGTGTGT

Variant names:

• chr6-55759124-T-TACACACAC
• rs749127959
• NM_021073.4:c.1105-17_1105-10dupGTGTGTGT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_021073.4(BMP5):​c.1105-17_1105-10dupGTGTGTGT 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 0.0010 (0 hom., cov: 18)
  • Exomes 𝑓: 0.0024 (39 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 54 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP5	NM_021073.4	c.1105-17_1105-10dupGTGTGTGT		intron_variant	Intron 5 of 6	ENST00000370830.4	NP_066551.1
BMP5	NM_001329754.2	c.1104+1325_1104+1332dupGTGTGTGT		intron_variant	Intron 5 of 5		NP_001316683.1
BMP5	NM_001329756.2	c.1028-3450_1028-3443dupGTGTGTGT		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_1105-9insGTGTGTGT		intron_variant	Intron 5 of 6	1	NM_021073.4	ENSP00000359866.3

Frequencies

GnomAD3 genomes AF: 0.000996 AC: 54 AN: 54200 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00221

Gnomad EAS AF: 0.00225

Gnomad SAS AF: 0.000680

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000788

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000800 AC: 171 AN: 213682 Hom.: 18 AF XY: 0.000773 AC XY: 90 AN XY: 116414

Gnomad AFR exome AF: 0.00120

Gnomad AMR exome AF: 0.000657

Gnomad ASJ exome AF: 0.000555

Gnomad EAS exome AF: 0.00140

Gnomad SAS exome AF: 0.000330

Gnomad FIN exome AF: 0.000284

Gnomad NFE exome AF: 0.000920

Gnomad OTH exome AF: 0.000767

GnomAD4 exome AF: 0.00241 AC: 921 AN: 382938 Hom.: 39 Cov.: 0 AF XY: 0.00233 AC XY: 504 AN XY: 216712

Gnomad4 AFR exome AF: 0.00145

Gnomad4 AMR exome AF: 0.00102

Gnomad4 ASJ exome AF: 0.00229

Gnomad4 EAS exome AF: 0.00176

Gnomad4 SAS exome AF: 0.000853

Gnomad4 FIN exome AF: 0.00303

Gnomad4 NFE exome AF: 0.00315

Gnomad4 OTH exome AF: 0.00244

GnomAD4 genome AF: 0.000996 AC: 54 AN: 54230 Hom.: 0 Cov.: 18 AF XY: 0.000753 AC XY: 18 AN XY: 23896

Gnomad4 AFR AF: 0.00152

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00221

Gnomad4 EAS AF: 0.00225

Gnomad4 SAS AF: 0.000681

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000788

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;