rs544280047

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004281.4(BAG3):c.-294A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 293,682 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 1 hom. )

Consequence

BAG3
NM_004281.4 5_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 0.0280

Publications

1 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 10-119651382-A-C is Benign according to our data. Variant chr10-119651382-A-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 298947.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00266 (404/152076) while in subpopulation NFE AF = 0.00505 (343/67930). AF 95% confidence interval is 0.00461. There are 0 homozygotes in GnomAd4. There are 175 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 404 AD 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.-294A>C		5_prime_UTR	Exon 1 of 4	NP_004272.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BAG3	ENST00000369085.8	TSL:1 MANE Select	c.-294A>C	5_prime_UTR	Exon 1 of 4	ENSP00000358081.4	O95817
BAG3	ENST00000889978.1		c.-294A>C	5_prime_UTR	Exon 1 of 4	ENSP00000560037.1
BAG3	ENST00000889980.1		c.-294A>C	5_prime_UTR	Exon 1 of 4	ENSP00000560039.1

Frequencies

GnomAD3 genomes

AF:

0.00266

AC:

404

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000757

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00505

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.00327

AC:

463

AN:

141606

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

231

AN XY:

71818

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

3906

American (AMR)

AF:

0.00

AC:

AN:

3640

Ashkenazi Jewish (ASJ)

AF:

0.000397

AC:

AN:

5044

East Asian (EAS)

AF:

0.00

AC:

AN:

11388

South Asian (SAS)

AF:

0.00

AC:

AN:

3466

European-Finnish (FIN)

AF:

0.000613

AC:

AN:

11414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

732

European-Non Finnish (NFE)

AF:

0.00468

AC:

434

AN:

92660

Other (OTH)

AF:

0.00171

AC:

AN:

9356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00266

AC:

404

AN:

152076

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41528

American (AMR)

AF:

0.00124

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000757

AC:

AN:

10572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00505

AC:

343

AN:

67930

Other (OTH)

AF:

0.00142

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00314

Hom.:

Bravo

AF:

0.00227

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Dilated cardiomyopathy 1HH (1)

Myofibrillar myopathy 6 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

0.028

PromoterAI

0.13

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(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

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