chr20-57171260-T-C

Position:

• chr20-57171260-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001719.3(BMP7):​c.1147-152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,124,550 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (50 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (26 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-57171260-T-C is Benign according to our data. Variant chr20-57171260-T-C is described in ClinVar as [Benign]. Clinvar id is 1273116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0145 (2212/152342) while in subpopulation AFR AF= 0.0503 (2089/41566). AF 95% confidence interval is 0.0485. There are 50 homozygotes in gnomad4. There are 1038 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2212 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3	c.1147-152A>G		intron_variant		ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8	c.1147-152A>G		intron_variant		1	NM_001719.3	P1
BMP7	ENST00000395864.7	c.949-152A>G		intron_variant		5
BMP7	ENST00000460817.5	n.647-152A>G		intron_variant, non_coding_transcript_variant		3
BMP7	ENST00000476877.1	n.391-152A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2210 AN: 152224 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00150 AC: 1454 AN: 972208 Hom.: 26 AF XY: 0.00119 AC XY: 591 AN XY: 495860

Gnomad4 AFR exome AF: 0.0479

Gnomad4 AMR exome AF: 0.00259

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000272

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000876

Gnomad4 OTH exome AF: 0.00357

GnomAD4 genome AF: 0.0145 AC: 2212 AN: 152342 Hom.: 50 Cov.: 33 AF XY: 0.0139 AC XY: 1038 AN XY: 74498

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.00542

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.0180 Hom.: 4

Bravo AF: 0.0161

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.66

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: rs16980799; hg19: chr20-55746316;