rs749127959

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-55759124-TACACACACACAC-T
• chr6-55759124-TACACACACACAC-TACACACACAC
• chr6-55759124-TACACACACACAC-TACACACACACACAC
• chr6-55759124-TACACACACACAC-TACACACACACACACAC
• chr6-55759124-TACACACACACAC-TACACACACACACACACAC
• chr6-55759124-TACACACACACAC-TACACACACACACACACACAC
• chr6-55759124-TACACACACACAC-TACACACACACACACACACACAC
• chr6-55759124-TACACACACACAC-TACACACACACACACACACACACAC
• chr6-55759124-TACACACACACAC-TACACACACACACACACACACACACAC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021073.4(BMP5):​c.1105-21_1105-10delGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 437,226 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 0.000018 (0 hom., cov: 12)
  • Exomes 𝑓: 0.0000026 (0 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP5	NM_021073.4	c.1105-21_1105-10delGTGTGTGTGTGT		intron_variant	Intron 5 of 6	ENST00000370830.4	NP_066551.1
BMP5	NM_001329754.2	c.1104+1321_1104+1332delGTGTGTGTGTGT		intron_variant	Intron 5 of 5		NP_001316683.1
BMP5	NM_001329756.2	c.1028-3454_1028-3443delGTGTGTGTGTGT		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.1105-21_1105-10delGTGTGTGTGTGT		intron_variant	Intron 5 of 6	1	NM_021073.4	ENSP00000359866.3

Frequencies

GnomAD3 genomes AF: 0.0000184 AC: 1 AN: 54204 Hom.: 0 Cov.: 12

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: 0.0000328

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000261 AC: 1 AN: 383022 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 216766

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000495

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000184 AC: 1 AN: 54204 Hom.: 0 Cov.: 12 AF XY: 0.0000419 AC XY: 1 AN XY: 23878

Gnomad4 AFR AF: 0.00

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: 0.0000328

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;