chr14-103557367-C-T

Variant names:

• chr14-103557367-C-T
• rs7693
• NM_001015048.3:c.*2454G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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]

BAG5 Gene-Disease associations (from GenCC):

• cardiomyopathy, dilated, 2F

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dilated cardiomyopathy

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ENSG00000258851 (HGNC:58460):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015048.3. 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
	BAG5	NM_001015048.3	MANE Select	c.*2454G>A		3_prime_UTR	Exon 2 of 2	NP_001015048.1	A0A024R6M6
	BAG5	NM_001015049.5		c.*2454G>A		3_prime_UTR	Exon 2 of 2	NP_001015049.2	A0A024R6M6
	BAG5	NM_004873.4		c.*2454G>A		3_prime_UTR	Exon 2 of 2	NP_004864.1	A0A024R6M6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG5	ENST00000299204.6	TSL:1 MANE Select	c.*2454G>A		3_prime_UTR	Exon 2 of 2	ENSP00000299204.4	Q9UL15-1
	BAG5	ENST00000445922.2	TSL:1	c.*2454G>A		3_prime_UTR	Exon 2 of 2	ENSP00000391713.2	Q9UL15-1
	ENSG00000258851	ENST00000556332.1	TSL:4	n.442+3505C>T		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.0897 AC: 3725 AN: 41508

American (AMR) AF: 0.244 AC: 3720 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1330 AN: 3472

East Asian (EAS) AF: 0.0823 AC: 427 AN: 5186

South Asian (SAS) AF: 0.260 AC: 1253 AN: 4816

European-Finnish (FIN) AF: 0.286 AC: 3019 AN: 10552

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24966 AN: 67970

Other (OTH) AF: 0.292 AC: 617 AN: 2116

Alfa AF: 0.326 Hom.: 13037

Bravo AF: 0.248

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7693; hg19: chr14-104023704;