10-119651468-C-T
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_004281.4(BAG3):c.-208C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 444,232 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0030 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00044 ( 0 hom. )
Consequence
BAG3
NM_004281.4 5_prime_UTR
NM_004281.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.04
Genes affected
BAG3 (HGNC:939): (BAG cochaperone 3) BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The protein encoded by this gene contains a WW domain in the N-terminal region and a BAG domain in the C-terminal region. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 10-119651468-C-T is Benign according to our data. Variant chr10-119651468-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1190806.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00298 (453/152214) while in subpopulation AFR AF= 0.0103 (429/41560). AF 95% confidence interval is 0.00952. There are 2 homozygotes in gnomad4. There are 231 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 453 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BAG3 | NM_004281.4 | c.-208C>T | 5_prime_UTR_variant | 1/4 | ENST00000369085.8 | NP_004272.2 | ||
BAG3 | XM_005270287.2 | c.-208C>T | 5_prime_UTR_variant | 1/4 | XP_005270344.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BAG3 | ENST00000369085.8 | c.-208C>T | 5_prime_UTR_variant | 1/4 | 1 | NM_004281.4 | ENSP00000358081 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00298 AC: 453AN: 152106Hom.: 2 Cov.: 33
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GnomAD4 exome AF: 0.000438 AC: 128AN: 292018Hom.: 0 Cov.: 4 AF XY: 0.000357 AC XY: 54AN XY: 151090
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GnomAD4 genome AF: 0.00298 AC: 453AN: 152214Hom.: 2 Cov.: 33 AF XY: 0.00310 AC XY: 231AN XY: 74428
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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 | GeneDx | Jul 07, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at