20-57169331-G-C

Variant names:

• chr20-57169331-G-C
• rs6025415
• NM_001719.3:c.*1628C>G

Variant summary

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

The ENST00000395863.8(BMP7):​c.*1628C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,172 control chromosomes in the GnomAD database, including 15,369 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 0.43 (15369 hom., cov: 33)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: BMP7 ENST00000395863.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395863.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	NM_001719.3	MANE Select	c.*1628C>G		3_prime_UTR	Exon 7 of 7	NP_001710.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	ENST00000395863.8	TSL:1 MANE Select	c.*1628C>G		3_prime_UTR	Exon 7 of 7	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65989 AN: 152040 Hom.: 15370 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.333 AC: 4 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.375 AC XY: 3 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.500 AC: 3 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.434 AC: 65998 AN: 152160 Hom.: 15369 Cov.: 33 AF XY: 0.436 AC XY: 32467 AN XY: 74390

African (AFR) AF: 0.263 AC: 10927 AN: 41500

American (AMR) AF: 0.422 AC: 6454 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1456 AN: 3472

East Asian (EAS) AF: 0.678 AC: 3507 AN: 5170

South Asian (SAS) AF: 0.333 AC: 1605 AN: 4814

European-Finnish (FIN) AF: 0.576 AC: 6100 AN: 10596

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34323 AN: 67998

Other (OTH) AF: 0.425 AC: 898 AN: 2114

Alfa AF: 0.337 Hom.: 946

Bravo AF: 0.422

Asia WGS AF: 0.434 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.11
DANN	Benign	0.40
PhyloP100		-0.58
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: rs6025415; hg19: chr20-55744387;