chr20-57173048-A-AT

Position:

• chr20-57173048-A-AT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001719.3(BMP7):​c.1146+151_1146+152insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 741,768 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00083 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (3 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.309

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 20-57173048-A-AT is Benign according to our data. Variant chr20-57173048-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 1315742.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 126 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3	c.1146+151_1146+152insA		intron_variant		ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8	c.1146+151_1146+152insA		intron_variant		1	NM_001719.3	P1

Frequencies

GnomAD3 genomes AF: 0.000832 AC: 126 AN: 151454 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00960

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000354

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00284 AC: 1679 AN: 590202 Hom.: 3 Cov.: 8 AF XY: 0.00272 AC XY: 849 AN XY: 312706

Gnomad4 AFR exome AF: 0.00177

Gnomad4 AMR exome AF: 0.00131

Gnomad4 ASJ exome AF: 0.00133

Gnomad4 EAS exome AF: 0.000356

Gnomad4 SAS exome AF: 0.00127

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.00277

Gnomad4 OTH exome AF: 0.00185

GnomAD4 genome AF: 0.000831 AC: 126 AN: 151566 Hom.: 1 Cov.: 33 AF XY: 0.00113 AC XY: 84 AN XY: 74058

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00960

Gnomad4 NFE AF: 0.000354

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs200005274; hg19: chr20-55748104;