20-57256157-T-C

Variant names:

• chr20-57256157-T-C
• rs6025469
• NM_001719.3:c.418+9548A>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.418+9548A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,966 control chromosomes in the GnomAD database, including 12,679 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 0.40 (12679 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• 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 = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.418+9548A>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.418+9548A>G		intron_variant	Intron 1 of 6	1	NM_001719.3	ENSP00000379204.3
BMP7	ENST00000450594.6	c.418+9548A>G		intron_variant	Intron 1 of 5	2		ENSP00000398687.2
BMP7	ENST00000395864.7	c.418+9548A>G		intron_variant	Intron 1 of 5	5		ENSP00000379205.3
BMP7	ENST00000433911.1	c.73+9548A>G		intron_variant	Intron 1 of 6	5		ENSP00000390814.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61011 AN: 151848 Hom.: 12655 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.402 AC: 61081 AN: 151966 Hom.: 12679 Cov.: 33 AF XY: 0.403 AC XY: 29898 AN XY: 74266

African (AFR) AF: 0.509 AC: 21080 AN: 41418

American (AMR) AF: 0.443 AC: 6767 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1142 AN: 3466

East Asian (EAS) AF: 0.249 AC: 1288 AN: 5168

South Asian (SAS) AF: 0.366 AC: 1764 AN: 4820

European-Finnish (FIN) AF: 0.371 AC: 3912 AN: 10548

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23958 AN: 67966

Other (OTH) AF: 0.393 AC: 829 AN: 2112

Alfa AF: 0.355 Hom.: 1954

Bravo AF: 0.411

Asia WGS AF: 0.341 AC: 1188 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	0.14
DANN	Benign	0.81
PhyloP100		-2.2
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: rs6025469; hg19: chr20-55831213;