10-119651626-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004281.4(BAG3):c.-50C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,458,480 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (1 hom.)
• Consequence: BAG3 NM_004281.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.33

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-119651626-C-T is Benign according to our data. Variant chr10-119651626-C-T is described in ClinVar as [Benign]. Clinvar id is 201678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00103 (157/151980) while in subpopulation AFR AF= 0.00352 (146/41490). AF 95% confidence interval is 0.00305. There are 2 homozygotes in gnomad4. There are 78 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 154 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAG3	NM_004281.4	c.-50C>T		5_prime_UTR_variant	1/4	ENST00000369085.8
BAG3	XM_005270287.2	c.-50C>T		5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG3	ENST00000369085.8	c.-50C>T		5_prime_UTR_variant	1/4	1	NM_004281.4	P1

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 154 AN: 151872 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000139 AC: 16 AN: 115222 Hom.: 0 AF XY: 0.000166 AC XY: 11 AN XY: 66364

Gnomad AFR exome AF: 0.00299

Gnomad AMR exome AF: 0.000118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000121

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000399

GnomAD4 exome AF: 0.000103 AC: 134 AN: 1306500 Hom.: 1 Cov.: 30 AF XY: 0.0000933 AC XY: 60 AN XY: 643216

Gnomad4 AFR exome AF: 0.00338

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000447

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000677

Gnomad4 OTH exome AF: 0.000453

GnomAD4 genome AF: 0.00103 AC: 157 AN: 151980 Hom.: 2 Cov.: 33 AF XY: 0.00105 AC XY: 78 AN XY: 74310

Gnomad4 AFR AF: 0.00352

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.00121

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 02, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.3
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs527696524; hg19: chr10-121411138; COSMIC: COSV100958224; COSMIC: COSV100958224;