rs6099486

Variant names:

• chr20-57174515-T-C
• rs6099486
• NM_001719.3:c.1035+416A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001719.3(BMP7):​c.1035+416A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,840 control chromosomes in the GnomAD database, including 20,560 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 0.52 (20560 hom., cov: 32)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789
• Publications: 4 publications found

Genes affected

BMP7 (HGNC:1074): (bone morphogenetic protein 7) 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, kidney and brown adipose tissue development. Additionally, this protein induces ectopic bone formation and may promote fracture healing in human patients. [provided by RefSeq, Jul 2016]

BMP7 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• hypospadias

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.1035+416A>G		intron_variant	Intron 5 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.1035+416A>G		intron_variant	Intron 5 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78355 AN: 151722 Hom.: 20521 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.530

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.517 AC: 78462 AN: 151840 Hom.: 20560 Cov.: 32 AF XY: 0.516 AC XY: 38307 AN XY: 74178

African (AFR) AF: 0.579 AC: 23945 AN: 41390

American (AMR) AF: 0.556 AC: 8489 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1964 AN: 3466

East Asian (EAS) AF: 0.314 AC: 1612 AN: 5134

South Asian (SAS) AF: 0.645 AC: 3091 AN: 4794

European-Finnish (FIN) AF: 0.422 AC: 4446 AN: 10530

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33387 AN: 67930

Other (OTH) AF: 0.534 AC: 1127 AN: 2112

Alfa AF: 0.501 Hom.: 2438

Bravo AF: 0.523

Asia WGS AF: 0.536 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.28
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6099486; hg19: chr20-55749571;