chr20-57228631-C-T

Variant names:

• chr20-57228631-C-T
• rs17404303
• NM_001719.3:c.419-210G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001719.3(BMP7):​c.419-210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,032 control chromosomes in the GnomAD database, including 9,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (9169 hom., cov: 32)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305
• Publications: 11 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-57228631-C-T is Benign according to our data. Variant chr20-57228631-C-T is described in ClinVar as Benign. ClinVar VariationId is 667563.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	NM_001719.3	MANE Select	c.419-210G>A		intron	N/A	NP_001710.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	ENST00000395863.8	TSL:1 MANE Select	c.419-210G>A		intron	N/A	ENSP00000379204.3
	BMP7	ENST00000450594.6	TSL:2	c.419-210G>A		intron	N/A	ENSP00000398687.2
	BMP7	ENST00000395864.7	TSL:5	c.419-210G>A		intron	N/A	ENSP00000379205.3

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48374 AN: 151916 Hom.: 9171 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.318 AC: 48402 AN: 152032 Hom.: 9169 Cov.: 32 AF XY: 0.324 AC XY: 24037 AN XY: 74292

African (AFR) AF: 0.132 AC: 5480 AN: 41512

American (AMR) AF: 0.312 AC: 4760 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3468

East Asian (EAS) AF: 0.0382 AC: 198 AN: 5182

South Asian (SAS) AF: 0.398 AC: 1915 AN: 4806

European-Finnish (FIN) AF: 0.452 AC: 4775 AN: 10566

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28742 AN: 67916

Other (OTH) AF: 0.330 AC: 694 AN: 2106

Alfa AF: 0.389 Hom.: 50805

Bravo AF: 0.293

Asia WGS AF: 0.183 AC: 637 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.70
PhyloP100		0.30
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: rs17404303; hg19: chr20-55803687;