10-119651626-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004281.4(BAG3):​c.-50C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,458,480 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

BAG3
NM_004281.4 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.33

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 10-119651626-C-T is Benign according to our data. Variant chr10-119651626-C-T is described in ClinVar as [Benign]. Clinvar id is 201678.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00103 (157/151980) while in subpopulation AFR AF = 0.00352 (146/41490). AF 95% confidence interval is 0.00305. There are 2 homozygotes in GnomAd4. There are 78 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High AC in GnomAd4 at 157 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BAG3NM_004281.4 linkc.-50C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 4 ENST00000369085.8 NP_004272.2 O95817
BAG3NM_004281.4 linkc.-50C>T 5_prime_UTR_variant Exon 1 of 4 ENST00000369085.8 NP_004272.2 O95817
BAG3XM_005270287.2 linkc.-50C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 4 XP_005270344.1
BAG3XM_005270287.2 linkc.-50C>T 5_prime_UTR_variant Exon 1 of 4 XP_005270344.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BAG3ENST00000369085.8 linkc.-50C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 4 1 NM_004281.4 ENSP00000358081.4 O95817
BAG3ENST00000369085.8 linkc.-50C>T 5_prime_UTR_variant Exon 1 of 4 1 NM_004281.4 ENSP00000358081.4 O95817

Frequencies

GnomAD3 genomes
AF:
0.00101
AC:
154
AN:
151872
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00346
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
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:
0.0000147
Gnomad OTH
AF:
0.000958
GnomAD2 exomes
AF:
0.000139
AC:
16
AN:
115222
AF XY:
0.000166
show subpopulations
Gnomad AFR exome
AF:
0.00299
Gnomad AMR exome
AF:
0.000118
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000399
GnomAD4 exome
AF:
0.000103
AC:
134
AN:
1306500
Hom.:
1
Cov.:
30
AF XY:
0.0000933
AC XY:
60
AN XY:
643216
show subpopulations
African (AFR)
AF:
0.00338
AC:
90
AN:
26624
American (AMR)
AF:
0.000224
AC:
6
AN:
26756
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21164
East Asian (EAS)
AF:
0.00
AC:
0
AN:
28748
South Asian (SAS)
AF:
0.0000447
AC:
3
AN:
67178
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45290
Middle Eastern (MID)
AF:
0.000889
AC:
4
AN:
4500
European-Non Finnish (NFE)
AF:
0.00000677
AC:
7
AN:
1033222
Other (OTH)
AF:
0.000453
AC:
24
AN:
53018
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.511
Heterozygous variant carriers
0
6
12
18
24
30
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00103
AC:
157
AN:
151980
Hom.:
2
Cov.:
33
AF XY:
0.00105
AC XY:
78
AN XY:
74310
show subpopulations
African (AFR)
AF:
0.00352
AC:
146
AN:
41490
American (AMR)
AF:
0.000523
AC:
8
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5132
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10568
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67902
Other (OTH)
AF:
0.000948
AC:
2
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
10
20
30
40
50
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000285
Hom.:
0
Bravo
AF:
0.00121

ClinVar

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

Submissions by phenotype

not specified Benign:1
Sep 02, 2014
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
8.3
DANN
Benign
0.88
PhyloP100
-2.3
PromoterAI
-0.048
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Mutation Taster
=300/0
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: rs527696524; hg19: chr10-121411138; COSMIC: COSV100958224; COSMIC: COSV100958224; API