Variant rs8946 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004281.4(BAG3):c.*218G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 674,268 control chromosomes in the GnomAD database, including 46,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 10280 hom., cov: 32)

Exomes 𝑓: 0.36 ( 35836 hom. )

Consequence

BAG3
NM_004281.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.516

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 10-119677500-G-C is Benign according to our data. Variant chr10-119677500-G-C is described in ClinVar as [Benign]. Clinvar id is 298966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAG3	NM_004281.4 linkuse as main transcript	c.*218G>C		3_prime_UTR_variant	4/4	ENST00000369085.8	NP_004272.2
BAG3	XM_005270287.2 linkuse as main transcript	c.*218G>C		3_prime_UTR_variant	4/4		XP_005270344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAG3	ENST00000369085.8 linkuse as main transcript	c.*218G>C		3_prime_UTR_variant	4/4	1	NM_004281.4	ENSP00000358081	P1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

55659

AN:

145814

Hom.:

10260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.295

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.382

GnomAD4 exome

AF:

0.364

AC:

192557

AN:

528338

Hom.:

35836

Cov.:

AF XY:

0.363

AC XY:

100605

AN XY:

277516

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.341

Gnomad4 ASJ exome

AF:

0.311

Gnomad4 EAS exome

AF:

0.342

Gnomad4 SAS exome

AF:

0.329

Gnomad4 FIN exome

AF:

0.320

Gnomad4 NFE exome

AF:

0.379

Gnomad4 OTH exome

AF:

0.362

GnomAD4 genome

AF:

0.382

AC:

55720

AN:

145930

Hom.:

10280

Cov.:

AF XY:

0.378

AC XY:

26862

AN XY:

71082

show subpopulations

Gnomad4 AFR

AF:

0.398

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.329

Gnomad4 EAS

AF:

0.363

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.336

Gnomad4 NFE

AF:

0.386

Gnomad4 OTH

AF:

0.383

Alfa

AF:

0.375

Hom.:

1299

Bravo

AF:

0.373

Asia WGS

AF:

0.306

AC:

1064

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	This variant is associated with the following publications: (PMID: 26512958) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Myofibrillar myopathy 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Myofibrillar myopathy 6;C3151293:Dilated cardiomyopathy 1HH

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Dilated cardiomyopathy 1HH

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.7

DANN

Benign

0.83

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over