rs193044

Variant names:

• chr20-57229060-A-C
• rs193044
• NM_001719.3:c.419-639T>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.419-639T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,126 control chromosomes in the GnomAD database, including 35,980 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 0.67 (35980 hom., cov: 32)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 2 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 (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.419-639T>G		intron_variant	Intron 1 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.419-639T>G		intron_variant	Intron 1 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101918 AN: 152008 Hom.: 35917 Cov.: 32

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.671 AC: 102041 AN: 152126 Hom.: 35980 Cov.: 32 AF XY: 0.668 AC XY: 49643 AN XY: 74348

African (AFR) AF: 0.907 AC: 37657 AN: 41526

American (AMR) AF: 0.624 AC: 9537 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2023 AN: 3468

East Asian (EAS) AF: 0.368 AC: 1901 AN: 5170

South Asian (SAS) AF: 0.608 AC: 2928 AN: 4816

European-Finnish (FIN) AF: 0.571 AC: 6043 AN: 10576

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.586 AC: 39820 AN: 67970

Other (OTH) AF: 0.659 AC: 1393 AN: 2114

Alfa AF: 0.640 Hom.: 4229

Bravo AF: 0.680

Asia WGS AF: 0.520 AC: 1809 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	8.4
DANN	Benign	0.66
PhyloP100		0.34
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: rs193044; hg19: chr20-55804116;