Genetic Variant NM_001387994.1:c.3394-108T>C (chr6-31639334-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001387994.1(BAG6):c.3394-108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,434,778 control chromosomes in the GnomAD database, including 3,534 homozygotes. 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: 𝑓 0.077 ( 649 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2885 hom. )

Consequence

BAG6
NM_001387994.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

Publications

12 publications found

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]

BAG6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387994.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BAG6	NM_001387994.1	MANE Select	c.3394-108T>C	intron	N/A	NP_001374923.1	P46379-3
BAG6	NM_001388012.1		c.3421-108T>C	intron	N/A	NP_001374941.1
BAG6	NM_001387989.1		c.3394-108T>C	intron	N/A	NP_001374918.1	P46379-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BAG6	ENST00000676615.2	MANE Select	c.3394-108T>C	intron	N/A	ENSP00000502941.1	P46379-3
BAG6	ENST00000211379.9	TSL:1	c.3286-108T>C	intron	N/A	ENSP00000211379.5	P46379-2
BAG6	ENST00000375976.8	TSL:1	c.3286-108T>C	intron	N/A	ENSP00000365143.4	P46379-2

Frequencies

GnomAD3 genomes

AF:

0.0767

AC:

11658

AN:

151980

Hom.:

648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0972

Gnomad ASJ

AF:

0.0435

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.00643

Gnomad FIN

AF:

0.00482

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0582

Gnomad OTH

AF:

0.0833

GnomAD4 exome

AF:

0.0597

AC:

76578

AN:

1282680

Hom.:

2885

Cov.:

AF XY:

0.0571

AC XY:

36519

AN XY:

639432

show subpopulations

African (AFR)

AF:

0.138

AC:

4038

AN:

29174

American (AMR)

AF:

0.0671

AC:

2632

AN:

39252

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

910

AN:

22098

East Asian (EAS)

AF:

0.000908

AC:

AN:

38554

South Asian (SAS)

AF:

0.00851

AC:

653

AN:

76754

European-Finnish (FIN)

AF:

0.00776

AC:

397

AN:

51172

Middle Eastern (MID)

AF:

0.0321

AC:

149

AN:

4648

European-Non Finnish (NFE)

AF:

0.0668

AC:

64633

AN:

967306

Other (OTH)

AF:

0.0583

AC:

3131

AN:

53722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

3613

7227

10840

14454

18067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2486

4972

7458

9944

12430

<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:

0.0766

AC:

11656

AN:

152098

Hom.:

649

Cov.:

AF XY:

0.0728

AC XY:

5414

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.139

AC:

5761

AN:

41474

American (AMR)

AF:

0.0971

AC:

1483

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0435

AC:

151

AN:

3470

East Asian (EAS)

AF:

0.00270

AC:

AN:

5178

South Asian (SAS)

AF:

0.00623

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00482

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0582

AC:

3957

AN:

67992

Other (OTH)

AF:

0.0820

AC:

173

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

545

1090

1634

2179

2724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0688

Hom.:

953

Bravo

AF:

0.0888

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.5

(source)

DANN

Benign

0.74

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over