NM_021073.4:c.1105-13_1105-10dupGTGT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_021073.4(BMP5):​c.1105-13_1105-10dupGTGT 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 0.029 (110 hom., cov: 18)
  • Exomes 𝑓: 0.023 (451 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0288 (1561/54198) while in subpopulation EAS AF= 0.0377 (67/1776). AF 95% confidence interval is 0.0345. There are 110 homozygotes in gnomad4. There are 667 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1561 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP5	NM_021073.4	c.1105-13_1105-10dupGTGT		intron_variant	Intron 5 of 6	ENST00000370830.4	NP_066551.1
BMP5	NM_001329754.2	c.1104+1329_1104+1332dupGTGT		intron_variant	Intron 5 of 5		NP_001316683.1
BMP5	NM_001329756.2	c.1028-3446_1028-3443dupGTGT		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_1105-9insGTGT		intron_variant	Intron 5 of 6	1	NM_021073.4	ENSP00000359866.3

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 1558 AN: 54170 Hom.: 110 Cov.: 18

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0277

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.0215

Gnomad EAS AF: 0.0377

Gnomad SAS AF: 0.00748

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.0152

Gnomad NFE AF: 0.0363

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00832 AC: 1778 AN: 213682 Hom.: 119 AF XY: 0.00809 AC XY: 942 AN XY: 116414

Gnomad AFR exome AF: 0.00556

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.00555

Gnomad EAS exome AF: 0.0193

Gnomad SAS exome AF: 0.00327

Gnomad FIN exome AF: 0.00298

Gnomad NFE exome AF: 0.00875

Gnomad OTH exome AF: 0.00824

GnomAD4 exome AF: 0.0229 AC: 8773 AN: 382636 Hom.: 451 Cov.: 0 AF XY: 0.0222 AC XY: 4817 AN XY: 216548

Gnomad4 AFR exome AF: 0.0124

Gnomad4 AMR exome AF: 0.0128

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.0386

Gnomad4 SAS exome AF: 0.00569

Gnomad4 FIN exome AF: 0.0178

Gnomad4 NFE exome AF: 0.0300

Gnomad4 OTH exome AF: 0.0276

GnomAD4 genome AF: 0.0288 AC: 1561 AN: 54198 Hom.: 110 Cov.: 18 AF XY: 0.0279 AC XY: 667 AN XY: 23890

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0235

Gnomad4 ASJ AF: 0.0215

Gnomad4 EAS AF: 0.0377

Gnomad4 SAS AF: 0.00749

Gnomad4 FIN AF: 0.00612

Gnomad4 NFE AF: 0.0363

Gnomad4 OTH AF: 0.0174

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;