10-119670135-AGCG-AGCGGCG

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The NM_004281.4(BAG3):c.474_476dupGGC(p.Ala159dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,612,550 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 17 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 7 hom. )

Consequence

BAG3
NM_004281.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 1.49

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: Unknown, AD Classification: DEFINITIVE Submitted by: ClinGen, G2P
myofibrillar myopathy 6
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
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

BAG3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_004281.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 10-119670135-A-AGCG is Benign according to our data. Variant chr10-119670135-A-AGCG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00742 (1130/152318) while in subpopulation AFR AF = 0.0263 (1092/41568). AF 95% confidence interval is 0.025. There are 17 homozygotes in GnomAd4. There are 518 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1130 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004281.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG3	NM_004281.4	MANE Select	c.474_476dupGGC	p.Ala159dup	disruptive_inframe_insertion	Exon 2 of 4	NP_004272.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAG3	ENST00000369085.8	TSL:1 MANE Select	c.474_476dupGGC	p.Ala159dup	disruptive_inframe_insertion	Exon 2 of 4	ENSP00000358081.4	O95817
BAG3	ENST00000889977.1		c.474_476dupGGC	p.Ala159dup	disruptive_inframe_insertion	Exon 3 of 5	ENSP00000560036.1
BAG3	ENST00000889978.1		c.474_476dupGGC	p.Ala159dup	disruptive_inframe_insertion	Exon 2 of 4	ENSP00000560037.1

Frequencies

GnomAD3 genomes

AF:

0.00737

AC:

1121

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00173

AC:

428

AN:

247306

AF XY:

0.00132

show subpopulations

Gnomad AFR exome

AF:

0.0255

Gnomad AMR exome

AF:

0.000811

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:

0.000659

GnomAD4 exome

AF:

0.000723

AC:

1056

AN:

1460232

Hom.:

Cov.:

AF XY:

0.000593

AC XY:

431

AN XY:

726318

show subpopulations

African (AFR)

AF:

0.0269

AC:

899

AN:

33474

American (AMR)

AF:

0.00107

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52662

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111294

Other (OTH)

AF:

0.00152

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

134

200

267

334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00742

AC:

1130

AN:

152318

Hom.:

Cov.:

AF XY:

0.00696

AC XY:

518

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0263

AC:

1092

AN:

41568

American (AMR)

AF:

0.00131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68018

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

116

175

233

291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00369

Hom.:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

not provided (4)

Cardiomyopathy (1)

Dilated Cardiomyopathy, Dominant (1)

Myofibrillar myopathy 6;C3151293:Dilated cardiomyopathy 1HH (1)

Myofibrillar Myopathy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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