chr20-57174725-A-G

Variant names:

• chr20-57174725-A-G
• rs6025422
• NM_001719.3:c.1035+206T>C

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.1035+206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,054 control chromosomes in the GnomAD database, including 21,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (21169 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.724
• 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=-0.91).
• BP6: Variant 20-57174725-A-G is Benign according to our data. Variant chr20-57174725-A-G is described in ClinVar as [Benign]. Clinvar id is 1258246.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.1035+206T>C		intron_variant	Intron 5 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.1035+206T>C		intron_variant	Intron 5 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79418 AN: 151936 Hom.: 21127 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.523 AC: 79528 AN: 152054 Hom.: 21169 Cov.: 33 AF XY: 0.522 AC XY: 38799 AN XY: 74328

African (AFR) AF: 0.604 AC: 25048 AN: 41454

American (AMR) AF: 0.560 AC: 8546 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1954 AN: 3472

East Asian (EAS) AF: 0.312 AC: 1614 AN: 5172

South Asian (SAS) AF: 0.645 AC: 3107 AN: 4820

European-Finnish (FIN) AF: 0.417 AC: 4408 AN: 10572

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33308 AN: 67976

Other (OTH) AF: 0.542 AC: 1143 AN: 2108

Alfa AF: 0.512 Hom.: 32576

Bravo AF: 0.532

Asia WGS AF: 0.538 AC: 1874 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		-0.72
Mutation Taster		=23/77	disease causing

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: rs6025422; hg19: chr20-55749781;