14-103557367-C-T

Variant summary

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

The NM_001015048.3(BAG5):c.*2454G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,098 control chromosomes in the GnomAD database, including 6,276 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 0.26 (6275 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: BAG5 NM_001015048.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

Genes affected

BAG5 (HGNC:941): (BAG cochaperone 5) The protein encoded by this gene is a member of the BAG1-related protein family. BAG1 is an anti-apoptotic protein that functions through interactions with a variety of cell apoptosis and growth related proteins including BCL-2, Raf-protein kinase, steroid hormone receptors, growth factor receptors and members of the heat shock protein 70 kDa family. This protein contains a BAG domain near the C-terminus, which could bind and inhibit the chaperone activity of Hsc70/Hsp70. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAG5	NM_001015048.3	c.*2454G>A		3_prime_UTR_variant	2/2	ENST00000299204.6
BAG5	NM_001015049.5	c.*2454G>A		3_prime_UTR_variant	2/2
BAG5	NM_004873.4	c.*2454G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG5	ENST00000299204.6	c.*2454G>A		3_prime_UTR_variant	2/2	1	NM_001015048.3	P1
BAG5	ENST00000445922.2	c.*2454G>A		3_prime_UTR_variant	2/2	1		P1
	ENST00000556332.1	n.442+3505C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39471 AN: 151976 Hom.: 6276 Cov.: 32

Gnomad AFR AF: 0.0900

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.259 AC: 39455 AN: 152096 Hom.: 6275 Cov.: 32 AF XY: 0.256 AC XY: 18997 AN XY: 74348

Gnomad4 AFR AF: 0.0897

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.0823

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.292

Alfa AF: 0.300 Hom.: 2378

Bravo AF: 0.248

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.1
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7693; hg19: chr14-104023704;