rs196335

chr10-119652349-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004281.4(BAG3):c.180+494C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 152,290 control chromosomes in the GnomAD database, including 700 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 0.089 (700 hom., cov: 33)
• Consequence: BAG3 NM_004281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.954

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAG3	NM_004281.4	c.180+494C>T		intron_variant		ENST00000369085.8
BAG3	XM_005270287.2	c.180+494C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG3	ENST00000369085.8	c.180+494C>T		intron_variant		1	NM_004281.4	P1

Frequencies

GnomAD3 genomes AF: 0.0895 AC: 13619 AN: 152172 Hom.: 701 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.0875

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0894 AC: 13622 AN: 152290 Hom.: 700 Cov.: 33 AF XY: 0.0844 AC XY: 6284 AN XY: 74478

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0688

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.0335

Gnomad4 NFE AF: 0.0997

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.0950 Hom.: 983

Bravo AF: 0.0955

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	7.2
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs196335; hg19: chr10-121411861;