10-119651468-C-T

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04
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]

Genome browser will be placed here

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
BAG3NM_004281.4 linkuse as main transcriptc.-208C>T 5_prime_UTR_variant 1/4 ENST00000369085.8 NP_004272.2
BAG3XM_005270287.2 linkuse as main transcriptc.-208C>T 5_prime_UTR_variant 1/4 XP_005270344.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BAG3ENST00000369085.8 linkuse as main transcriptc.-208C>T 5_prime_UTR_variant 1/41 NM_004281.4 ENSP00000358081 P1

Frequencies

GnomAD3 genomes
AF:
0.00298
AC:
453
AN:
152106
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0104
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.000959
GnomAD4 exome
AF:
0.000438
AC:
128
AN:
292018
Hom.:
0
Cov.:
4
AF XY:
0.000357
AC XY:
54
AN XY:
151090
show subpopulations
Gnomad4 AFR exome
AF:
0.0108
Gnomad4 AMR exome
AF:
0.00165
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000136
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000163
Gnomad4 OTH exome
AF:
0.000666
GnomAD4 genome
AF:
0.00298
AC:
453
AN:
152214
Hom.:
2
Cov.:
33
AF XY:
0.00310
AC XY:
231
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0103
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000949
Alfa
AF:
0.00201
Hom.:
0
Bravo
AF:
0.00323

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 submitterclinical testingGeneDxJul 07, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
CADD
Benign
19
DANN
Benign
0.72
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs529609887; hg19: chr10-121410980; API