chr6-55874255-A-G

Position:

• chr6-55874255-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021073.4(BMP5):​c.490+121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 1,273,494 control chromosomes in the GnomAD database, including 1,833 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (196 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1637 hom.)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP5	NM_021073.4	c.490+121T>C		intron_variant		ENST00000370830.4	NP_066551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP5	ENST00000370830.4	c.490+121T>C		intron_variant		1	NM_021073.4	ENSP00000359866	P1

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 5766 AN: 152062 Hom.: 196 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0913

Gnomad FIN AF: 0.0188

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0364

GnomAD4 exome AF: 0.0452 AC: 50699 AN: 1121314 Hom.: 1637 AF XY: 0.0466 AC XY: 26519 AN XY: 568650

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.0609

Gnomad4 ASJ exome AF: 0.0253

Gnomad4 EAS exome AF: 0.180

Gnomad4 SAS exome AF: 0.0836

Gnomad4 FIN exome AF: 0.0248

Gnomad4 NFE exome AF: 0.0379

Gnomad4 OTH exome AF: 0.0449

GnomAD4 genome AF: 0.0379 AC: 5771 AN: 152180 Hom.: 196 Cov.: 32 AF XY: 0.0386 AC XY: 2875 AN XY: 74402

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.0911

Gnomad4 FIN AF: 0.0188

Gnomad4 NFE AF: 0.0399

Gnomad4 OTH AF: 0.0380

Alfa AF: 0.0376 Hom.: 144

Bravo AF: 0.0387

Asia WGS AF: 0.118 AC: 408 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs3798818; hg19: chr6-55739053;