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GeneBe

6-31639644-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001387994.1(BAG6):c.3249G>A(p.Thr1083=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000706 in 1,607,742 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00045 ( 4 hom. )

Consequence

BAG6
NM_001387994.1 splice_region, synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.122
Variant links:
Genes affected
BAG6 (HGNC:13919): (BAG cochaperone 6) This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-31639644-C-T is Benign according to our data. Variant chr6-31639644-C-T is described in ClinVar as [Benign]. Clinvar id is 724730.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.122 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 485 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BAG6NM_001387994.1 linkuse as main transcriptc.3249G>A p.Thr1083= splice_region_variant, synonymous_variant 25/26 ENST00000676615.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BAG6ENST00000676615.2 linkuse as main transcriptc.3249G>A p.Thr1083= splice_region_variant, synonymous_variant 25/26 NM_001387994.1 A2P46379-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00319
AC:
485
AN:
152144
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00978
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00367
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00384
GnomAD3 exomes
AF:
0.00108
AC:
263
AN:
244188
Hom.:
2
AF XY:
0.00104
AC XY:
138
AN XY:
132922
show subpopulations
Gnomad AFR exome
AF:
0.00970
Gnomad AMR exome
AF:
0.000684
Gnomad ASJ exome
AF:
0.000309
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00176
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000290
Gnomad OTH exome
AF:
0.00101
GnomAD4 exome
AF:
0.000446
AC:
649
AN:
1455480
Hom.:
4
Cov.:
31
AF XY:
0.000518
AC XY:
375
AN XY:
723364
show subpopulations
Gnomad4 AFR exome
AF:
0.00784
Gnomad4 AMR exome
AF:
0.00112
Gnomad4 ASJ exome
AF:
0.0000386
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00224
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000749
Gnomad4 OTH exome
AF:
0.000883
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00319
AC:
486
AN:
152262
Hom.:
3
Cov.:
32
AF XY:
0.00298
AC XY:
222
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.00977
Gnomad4 AMR
AF:
0.00366
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00380
Alfa
AF:
0.00101
Hom.:
0
Bravo
AF:
0.00388
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000652

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
Cadd
Benign
9.7
Dann
Benign
0.89
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs148136430; hg19: chr6-31607421; API