rs2182435

Positions:

• chr20-57175148-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BMP7	NM_001719.3	c.959-141C>A		intron_variant		ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8	c.959-141C>A		intron_variant		1	NM_001719.3	P1

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

Gnomad4 AFR exome AF: 0.0549

Gnomad4 AMR exome AF: 0.0443

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.0203

Gnomad4 SAS exome AF: 0.0619

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0806

Gnomad4 OTH exome AF: 0.0808

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

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.0501

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0378

Gnomad4 SAS AF: 0.0676

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0805

Gnomad4 OTH AF: 0.0666

Alfa AF: 0.0728 Hom.: 96

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs2182435; hg19: chr20-55750204;