chr20-57174925-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001719.3(BMP7):c.1035+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,610,326 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0058 ( 12 hom., cov: 33)
Exomes 𝑓: 0.00074 ( 9 hom. )
Consequence
BMP7
NM_001719.3 splice_donor_region, intron
NM_001719.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001019
2
Clinical Significance
Conservation
PhyloP100: 0.339
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 20-57174925-C-T is Benign according to our data. Variant chr20-57174925-C-T is described in ClinVar as [Benign]. Clinvar id is 710158.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00585 (891/152338) while in subpopulation AFR AF= 0.0194 (806/41572). AF 95% confidence interval is 0.0183. There are 12 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 888 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMP7 | NM_001719.3 | c.1035+6G>A | splice_donor_region_variant, intron_variant | ENST00000395863.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMP7 | ENST00000395863.8 | c.1035+6G>A | splice_donor_region_variant, intron_variant | 1 | NM_001719.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00583 AC: 888AN: 152220Hom.: 12 Cov.: 33
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GnomAD3 exomes AF: 0.00158 AC: 391AN: 247284Hom.: 4 AF XY: 0.00122 AC XY: 163AN XY: 133822
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GnomAD4 exome AF: 0.000738 AC: 1076AN: 1457988Hom.: 9 Cov.: 32 AF XY: 0.000674 AC XY: 489AN XY: 725334
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at