GeneBe

10-119676443-A-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000369085.8(BAG3):​c.910-21A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BAG3
ENST00000369085.8 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.729

Publications

11 publications found
Variant links:
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]
BAG3 Gene-Disease associations (from GenCC):
  • dilated cardiomyopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • dilated cardiomyopathy 1HH
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • myofibrillar myopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, ClinGen
  • myofibrillar myopathy 6
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
  • familial isolated dilated cardiomyopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Charcot-Marie-tooth disease, axonal, type 2JJ
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • distal hereditary motor neuropathy
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369085.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
BAG3
NM_004281.4
MANE Select
c.910-21A>T
intron
N/ANP_004272.2

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
BAG3
ENST00000369085.8
TSL:1 MANE Select
c.910-21A>T
intron
N/AENSP00000358081.4
BAG3
ENST00000450186.1
TSL:5
c.736-24A>T
intron
N/AENSP00000410036.1
ENSG00000295480
ENST00000730378.1
n.405+465T>A
intron
N/A

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459626
Hom.:
0
Cov.:
37
AF XY:
0.00000138
AC XY:
1
AN XY:
726300
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33426
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26122
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39686
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86182
European-Finnish (FIN)
AF:
0.0000188
AC:
1
AN:
53274
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1110136
Other (OTH)
AF:
0.00
AC:
0
AN:
60318
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
5.6
DANN
Benign
0.75
PhyloP100
-0.73
Mutation Taster
=100/0
polymorphism

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: rs196294; hg19: chr10-121435955; API