chr20-57174993-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001719.3(BMP7):​c.973G>A​(p.Asp325Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000447 in 1,611,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

BMP7
NM_001719.3 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.78
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.27439243).
BS2
High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BMP7NM_001719.3 linkuse as main transcriptc.973G>A p.Asp325Asn missense_variant 5/7 ENST00000395863.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BMP7ENST00000395863.8 linkuse as main transcriptc.973G>A p.Asp325Asn missense_variant 5/71 NM_001719.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000201
AC:
5
AN:
248930
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134688
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000442
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000411
AC:
60
AN:
1459212
Hom.:
0
Cov.:
32
AF XY:
0.0000358
AC XY:
26
AN XY:
725992
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000513
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152212
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000660
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 20, 2021The c.973G>A (p.D325N) alteration is located in exon 5 (coding exon 5) of the BMP7 gene. This alteration results from a G to A substitution at nucleotide position 973, causing the aspartic acid (D) at amino acid position 325 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Uncertain
0.54
D;.;T
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Uncertain
0.091
D
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.61
T
MutationAssessor
Uncertain
2.6
M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Uncertain
0.42
Sift
Benign
0.36
T;T;T
Sift4G
Benign
0.39
T;T;T
Polyphen
0.0070
B;B;P
Vest4
0.40
MVP
0.84
MPC
0.66
ClinPred
0.66
D
GERP RS
5.1
Varity_R
0.24
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200825690; hg19: chr20-55750049; COSMIC: COSV67782455; COSMIC: COSV67782455; API