chr20-57183599-A-G

Variant names:

• chr20-57183599-A-G
• rs6070015
• NM_001719.3:c.958+123T>C

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+123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,280,450 control chromosomes in the GnomAD database, including 554,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (54874 hom., cov: 34)
  • Exomes 𝑓: 0.94 (499232 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0300
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 20-57183599-A-G is Benign according to our data. Variant chr20-57183599-A-G is described in ClinVar as Benign. ClinVar VariationId is 1241318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.958+123T>C		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.958+123T>C		intron_variant	Intron 4 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125902 AN: 152102 Hom.: 54866 Cov.: 34

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.871

GnomAD4 exome AF: 0.938 AC: 1058475 AN: 1128230 Hom.: 499232 AF XY: 0.941 AC XY: 537330 AN XY: 571108

African (AFR) AF: 0.506 AC: 13414 AN: 26494

American (AMR) AF: 0.951 AC: 37943 AN: 39890

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 22829 AN: 23732

East Asian (EAS) AF: 0.967 AC: 35502 AN: 36730

South Asian (SAS) AF: 0.964 AC: 74068 AN: 76796

European-Finnish (FIN) AF: 0.943 AC: 37857 AN: 40164

Middle Eastern (MID) AF: 0.931 AC: 3316 AN: 3560

European-Non Finnish (NFE) AF: 0.948 AC: 787977 AN: 831454

Other (OTH) AF: 0.922 AC: 45569 AN: 49410

GnomAD4 genome AF: 0.828 AC: 125965 AN: 152220 Hom.: 54874 Cov.: 34 AF XY: 0.832 AC XY: 61923 AN XY: 74460

African (AFR) AF: 0.521 AC: 21617 AN: 41472

American (AMR) AF: 0.918 AC: 14044 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3330 AN: 3472

East Asian (EAS) AF: 0.971 AC: 5038 AN: 5188

South Asian (SAS) AF: 0.964 AC: 4648 AN: 4824

European-Finnish (FIN) AF: 0.943 AC: 10015 AN: 10618

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64353 AN: 68030

Other (OTH) AF: 0.870 AC: 1838 AN: 2112

Alfa AF: 0.918 Hom.: 104803

Bravo AF: 0.814

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 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	-0.94
CADD	Benign	0.48
DANN	Benign	0.34
PhyloP100		-0.030
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: rs6070015; hg19: chr20-55758655;