6-55759124-TACACACACACAC-TACACACACACACACACAC

Variant names:

• chr6-55759124-T-TACACAC
• rs749127959
• NM_021073.4:c.1105-15_1105-10dupGTGTGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_021073.4(BMP5):​c.1105-15_1105-10dupGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (4 hom., cov: 18)
  • Exomes 𝑓: 0.0037 (70 hom.)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.73
• Publications: 0 publications found

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]

BMP5 Gene-Disease associations (from GenCC):

• dysostosis

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-55759124-T-TACACAC is Benign according to our data. Variant chr6-55759124-T-TACACAC is described in ClinVar as Benign. ClinVar VariationId is 735236.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0038 (206/54232) while in subpopulation EAS AF = 0.027 (48/1776). AF 95% confidence interval is 0.0209. There are 4 homozygotes in GnomAd4. There are 82 alleles in the male GnomAd4 subpopulation. Median coverage is 18. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021073.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP5	NM_021073.4	MANE Select	c.1105-15_1105-10dupGTGTGT		intron	N/A	NP_066551.1	P22003-1
	BMP5	NM_001329754.2		c.1104+1327_1104+1332dupGTGTGT		intron	N/A	NP_001316683.1	P22003-2
	BMP5	NM_001329756.2		c.1028-3448_1028-3443dupGTGTGT		intron	N/A	NP_001316685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP5	ENST00000370830.4	TSL:1 MANE Select	c.1105-10_1105-9insGTGTGT		intron	N/A	ENSP00000359866.3	P22003-1
	BMP5	ENST00000901523.1		c.1104+1332_1104+1333insGTGTGT		intron	N/A	ENSP00000571582.1

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 205 AN: 54202 Hom.: 4 Cov.: 18

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.00369

Gnomad AMR AF: 0.00398

Gnomad ASJ AF: 0.000552

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00153

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00325

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00181 AC: 387 AN: 213682 AF XY: 0.00163

Gnomad AFR exome AF: 0.000422

Gnomad AMR exome AF: 0.000986

Gnomad ASJ exome AF: 0.000555

Gnomad EAS exome AF: 0.0145

Gnomad FIN exome AF: 0.0000709

Gnomad NFE exome AF: 0.000665

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00367 AC: 1405 AN: 382928 Hom.: 70 Cov.: 0 AF XY: 0.00365 AC XY: 792 AN XY: 216714

African (AFR) AF: 0.00136 AC: 15 AN: 11010

American (AMR) AF: 0.00125 AC: 44 AN: 35268

Ashkenazi Jewish (ASJ) AF: 0.00126 AC: 16 AN: 12668

East Asian (EAS) AF: 0.0236 AC: 416 AN: 17598

South Asian (SAS) AF: 0.00282 AC: 165 AN: 58586

European-Finnish (FIN) AF: 0.00187 AC: 48 AN: 25736

Middle Eastern (MID) AF: 0.000490 AC: 1 AN: 2042

European-Non Finnish (NFE) AF: 0.00306 AC: 618 AN: 201968

Other (OTH) AF: 0.00454 AC: 82 AN: 18052

GnomAD4 genome AF: 0.00380 AC: 206 AN: 54232 Hom.: 4 Cov.: 18 AF XY: 0.00343 AC XY: 82 AN XY: 23898

African (AFR) AF: 0.00232 AC: 32 AN: 13788

American (AMR) AF: 0.00398 AC: 12 AN: 3018

Ashkenazi Jewish (ASJ) AF: 0.000552 AC: 1 AN: 1812

East Asian (EAS) AF: 0.0270 AC: 48 AN: 1776

South Asian (SAS) AF: 0.00477 AC: 7 AN: 1468

European-Finnish (FIN) AF: 0.00153 AC: 1 AN: 654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 66

European-Non Finnish (NFE) AF: 0.00325 AC: 99 AN: 30476

Other (OTH) AF: 0.00633 AC: 4 AN: 632

Alfa AF: 0.00162 Hom.: 31

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	BMP5-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs749127959; hg19: chr6-55623922;