chr20-57237222-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001719.3(BMP7):​c.419-8801T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,154 control chromosomes in the GnomAD database, including 36,380 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.68 ( 36380 hom., cov: 32)

Consequence

BMP7
NM_001719.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.923

Publications

6 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BMP7NM_001719.3 linkc.419-8801T>C intron_variant Intron 1 of 6 ENST00000395863.8 NP_001710.1 P18075A8K571

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BMP7ENST00000395863.8 linkc.419-8801T>C intron_variant Intron 1 of 6 1 NM_001719.3 ENSP00000379204.3 P18075

Frequencies

GnomAD3 genomes
AF:
0.675
AC:
102599
AN:
152036
Hom.:
36318
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.908
Gnomad AMI
AF:
0.609
Gnomad AMR
AF:
0.626
Gnomad ASJ
AF:
0.591
Gnomad EAS
AF:
0.369
Gnomad SAS
AF:
0.611
Gnomad FIN
AF:
0.585
Gnomad MID
AF:
0.623
Gnomad NFE
AF:
0.592
Gnomad OTH
AF:
0.662
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.675
AC:
102721
AN:
152154
Hom.:
36380
Cov.:
32
AF XY:
0.672
AC XY:
50020
AN XY:
74388
show subpopulations
African (AFR)
AF:
0.908
AC:
37695
AN:
41510
American (AMR)
AF:
0.626
AC:
9568
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.591
AC:
2052
AN:
3472
East Asian (EAS)
AF:
0.368
AC:
1908
AN:
5182
South Asian (SAS)
AF:
0.611
AC:
2947
AN:
4822
European-Finnish (FIN)
AF:
0.585
AC:
6194
AN:
10584
Middle Eastern (MID)
AF:
0.626
AC:
184
AN:
294
European-Non Finnish (NFE)
AF:
0.592
AC:
40221
AN:
67980
Other (OTH)
AF:
0.661
AC:
1397
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1596
3192
4789
6385
7981
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
788
1576
2364
3152
3940
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.614
Hom.:
14787
Bravo
AF:
0.684
Asia WGS
AF:
0.523
AC:
1817
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.63
DANN
Benign
0.31
PhyloP100
-0.92
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

Publications

Other links and lift over

dbSNP: rs162317; hg19: chr20-55812278; API