chr8-38176942-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_004874.4(BAG4):c.73G>A(p.Gly25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,555,586 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0029 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0037 ( 16 hom. )
Consequence
BAG4
NM_004874.4 missense
NM_004874.4 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 2.15
Genes affected
BAG4 (HGNC:940): (BAG cochaperone 4) The protein encoded by this gene is a member of the BAG1-related protein family. BAG1 is an anti-apoptotic protein that functions through interactions with a variety of cell apoptosis and growth related proteins including BCL-2, Raf-protein kinase, steroid hormone receptors, growth factor receptors and members of the heat shock protein 70 kDa family. This protein contains a BAG domain near the C-terminus, which could bind and inhibit the chaperone activity of Hsc70/Hsp70. This protein was found to be associated with the death domain of tumor necrosis factor receptor type 1 (TNF-R1) and death receptor-3 (DR3), and thereby negatively regulates downstream cell death signaling. The regulatory role of this protein in cell death was demonstrated in epithelial cells which undergo apoptosis while integrin mediated matrix contacts are lost. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.006784469).
BP6
Variant 8-38176942-G-A is Benign according to our data. Variant chr8-38176942-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658541.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 16 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BAG4 | NM_004874.4 | c.73G>A | p.Gly25Ser | missense_variant | 1/5 | ENST00000287322.5 | |
BAG4 | NM_001204878.2 | c.73G>A | p.Gly25Ser | missense_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAG4 | ENST00000287322.5 | c.73G>A | p.Gly25Ser | missense_variant | 1/5 | 1 | NM_004874.4 | P1 | |
BAG4 | ENST00000432471.6 | c.73G>A | p.Gly25Ser | missense_variant | 1/4 | 1 | |||
BAG4 | ENST00000521282.1 | n.58-63G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00295 AC: 449AN: 152258Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00350 AC: 567AN: 161938Hom.: 3 AF XY: 0.00353 AC XY: 304AN XY: 86098
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GnomAD4 exome AF: 0.00371 AC: 5203AN: 1403210Hom.: 16 Cov.: 31 AF XY: 0.00375 AC XY: 2595AN XY: 692716
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GnomAD4 genome AF: 0.00295 AC: 449AN: 152376Hom.: 1 Cov.: 33 AF XY: 0.00259 AC XY: 193AN XY: 74512
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | BAG4: BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Benign
T;T
Polyphen
0.85
.;P
Vest4
MVP
MPC
0.10
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at