chr20-57225881-C-T

Variant names:

• chr20-57225881-C-T
• rs6070031
• NM_001719.3:c.611+2348G>A

Variant summary

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

The NM_001719.3(BMP7):​c.611+2348G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 469,852 control chromosomes in the GnomAD database, including 38,352 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 0.36 (10532 hom., cov: 32)
  • Exomes 𝑓: 0.41 (27820 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 7 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 (REVEL=0.007).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001719.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	NM_001719.3	MANE Select	c.611+2348G>A		intron	N/A	NP_001710.1	A8K571

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	ENST00000395863.8	TSL:1 MANE Select	c.611+2348G>A		intron	N/A	ENSP00000379204.3	P18075
	BMP7	ENST00000433911.1	TSL:5	c.348G>A	p.Thr116Thr	synonymous	Exon 3 of 7	ENSP00000390814.1	H0Y4B5
	BMP7	ENST00000450594.6	TSL:2	c.611+2348G>A		intron	N/A	ENSP00000398687.2	B1AL00

Frequencies

GnomAD3 genomes AF: 0.358 AC: 53980 AN: 150944 Hom.: 10528 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.361

GnomAD2 exomes AF: 0.375 AC: 56266 AN: 149882 AF XY: 0.385

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.312

Gnomad ASJ exome AF: 0.418

Gnomad EAS exome AF: 0.0267

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.436

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.407 AC: 129870 AN: 318788 Hom.: 27820 Cov.: 0 AF XY: 0.413 AC XY: 74394 AN XY: 180126

African (AFR) AF: 0.235 AC: 1988 AN: 8466

American (AMR) AF: 0.311 AC: 8479 AN: 27266

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 4559 AN: 10790

East Asian (EAS) AF: 0.0293 AC: 270 AN: 9214

South Asian (SAS) AF: 0.440 AC: 26263 AN: 59730

European-Finnish (FIN) AF: 0.440 AC: 11941 AN: 27158

Middle Eastern (MID) AF: 0.469 AC: 1304 AN: 2780

European-Non Finnish (NFE) AF: 0.437 AC: 69467 AN: 159038

Other (OTH) AF: 0.390 AC: 5599 AN: 14346

GnomAD4 genome AF: 0.358 AC: 54021 AN: 151064 Hom.: 10532 Cov.: 32 AF XY: 0.361 AC XY: 26650 AN XY: 73850

African (AFR) AF: 0.238 AC: 9645 AN: 40548

American (AMR) AF: 0.330 AC: 5036 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3472

East Asian (EAS) AF: 0.0375 AC: 194 AN: 5174

South Asian (SAS) AF: 0.398 AC: 1920 AN: 4824

European-Finnish (FIN) AF: 0.461 AC: 4869 AN: 10562

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29730 AN: 67942

Other (OTH) AF: 0.357 AC: 750 AN: 2098

Alfa AF: 0.382 Hom.: 4829

Bravo AF: 0.333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.015
DANN	Benign	0.54
PhyloP100		-1.6
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: rs6070031; hg19: chr20-55800937; COSMIC: COSV67782543; COSMIC: COSV67782543;