chr20-57183506-C-T

Variant names:

• chr20-57183506-C-T
• rs76737492
• NM_001719.3:c.958+216G>A

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.958+216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 152,162 control chromosomes in the GnomAD database, including 465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.062 (465 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.154
• Publications: 0 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=-0.92).
• BP6: Variant 20-57183506-C-T is Benign according to our data. Variant chr20-57183506-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291873.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001719.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	NM_001719.3	MANE Select	c.958+216G>A		intron	N/A	NP_001710.1	A8K571

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	ENST00000395863.8	TSL:1 MANE Select	c.958+216G>A		intron	N/A	ENSP00000379204.3	P18075
	BMP7	ENST00000450594.6	TSL:2	c.958+216G>A		intron	N/A	ENSP00000398687.2	B1AL00
	BMP7	ENST00000395864.7	TSL:5	c.761-8499G>A		intron	N/A	ENSP00000379205.3	B1AKZ9

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9402 AN: 152044 Hom.: 463 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0378

Gnomad OTH AF: 0.0484

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

GnomAD4 genome AF: 0.0619 AC: 9424 AN: 152162 Hom.: 465 Cov.: 33 AF XY: 0.0608 AC XY: 4522 AN XY: 74394

African (AFR) AF: 0.130 AC: 5408 AN: 41482

American (AMR) AF: 0.0311 AC: 476 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.0284 AC: 147 AN: 5180

South Asian (SAS) AF: 0.0124 AC: 60 AN: 4832

European-Finnish (FIN) AF: 0.0502 AC: 531 AN: 10582

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0377 AC: 2567 AN: 68014

Other (OTH) AF: 0.0503 AC: 106 AN: 2108

Alfa AF: 0.0522 Hom.: 66

Bravo AF: 0.0639

Asia WGS AF: 0.0480 AC: 165 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs76737492; hg19: chr20-55758562;