20-57175148-G-T

Variant names:

• chr20-57175148-G-T
• rs2182435
• NM_001719.3:c.959-141C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001719.3(BMP7):​c.959-141C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 905,860 control chromosomes in the GnomAD database, including 2,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (433 hom., cov: 33)
  • Exomes 𝑓: 0.076 (2355 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-57175148-G-T is Benign according to our data. Variant chr20-57175148-G-T is described in ClinVar as [Benign]. Clinvar id is 1238833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.959-141C>A		intron_variant	Intron 4 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.959-141C>A		intron_variant	Intron 4 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10707 AN: 152140 Hom.: 433 Cov.: 33

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0502

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0805

Gnomad OTH AF: 0.0669

GnomAD4 exome AF: 0.0755 AC: 56929 AN: 753602 Hom.: 2355 AF XY: 0.0750 AC XY: 29524 AN XY: 393534

African (AFR) AF: 0.0549 AC: 1064 AN: 19386

American (AMR) AF: 0.0443 AC: 1535 AN: 34642

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2207 AN: 21056

East Asian (EAS) AF: 0.0203 AC: 662 AN: 32580

South Asian (SAS) AF: 0.0619 AC: 4084 AN: 65982

European-Finnish (FIN) AF: 0.100 AC: 3359 AN: 33576

Middle Eastern (MID) AF: 0.0677 AC: 275 AN: 4062

European-Non Finnish (NFE) AF: 0.0806 AC: 40747 AN: 505252

Other (OTH) AF: 0.0808 AC: 2996 AN: 37066

GnomAD4 genome AF: 0.0703 AC: 10710 AN: 152258 Hom.: 433 Cov.: 33 AF XY: 0.0705 AC XY: 5250 AN XY: 74448

African (AFR) AF: 0.0550 AC: 2284 AN: 41552

American (AMR) AF: 0.0501 AC: 767 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 388 AN: 3470

East Asian (EAS) AF: 0.0378 AC: 196 AN: 5186

South Asian (SAS) AF: 0.0676 AC: 326 AN: 4822

European-Finnish (FIN) AF: 0.100 AC: 1061 AN: 10602

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0805 AC: 5473 AN: 68006

Other (OTH) AF: 0.0666 AC: 141 AN: 2116

Alfa AF: 0.0721 Hom.: 151

Bravo AF: 0.0657

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 28, 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	-0.83
CADD	Benign	2.4
DANN	Benign	0.71
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2182435; hg19: chr20-55750204;