rs3787380

Variant names:

• chr20-57179054-T-C
• rs3787380
• NM_001719.3:c.959-4047A>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.959-4047A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,064 control chromosomes in the GnomAD database, including 9,950 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 0.35 (9950 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 8 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

ENSG00000293741 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.959-4047A>G		intron_variant	Intron 4 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.959-4047A>G		intron_variant	Intron 4 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52788 AN: 151946 Hom.: 9933 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.347 AC: 52839 AN: 152064 Hom.: 9950 Cov.: 33 AF XY: 0.349 AC XY: 25977 AN XY: 74338

African (AFR) AF: 0.215 AC: 8900 AN: 41462

American (AMR) AF: 0.480 AC: 7327 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1522 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1199 AN: 5160

South Asian (SAS) AF: 0.563 AC: 2709 AN: 4816

European-Finnish (FIN) AF: 0.304 AC: 3212 AN: 10582

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26737 AN: 67978

Other (OTH) AF: 0.400 AC: 845 AN: 2112

Alfa AF: 0.388 Hom.: 49442

Bravo AF: 0.350

Asia WGS AF: 0.395 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.70
PhyloP100		-0.38
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: rs3787380; hg19: chr20-55754110;