NM_004323.6:c.886-254A>C

Variant names:

• chr9-33256181-T-G
• rs706118
• NM_004323.6:c.886-254A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004323.6(BAG1):​c.886-254A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,074 control chromosomes in the GnomAD database, including 15,027 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 0.38 (15027 hom., cov: 32)
• Consequence: BAG1 NM_004323.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 7 publications found

Genes affected

BAG1 (HGNC:937): (BAG cochaperone 1) The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein encoded by this gene binds to BCL2 and is referred to as BCL2-associated athanogene. It enhances the anti-apoptotic effects of BCL2 and represents a link between growth factor receptors and anti-apoptotic mechanisms. Multiple protein isoforms are encoded by this mRNA through the use of a non-AUG (CUG) initiation codon, and three alternative downstream AUG initiation codons. A related pseudogene has been defined on chromosome X. [provided by RefSeq, Feb 2010]

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 (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG1	NM_004323.6	c.886-254A>C		intron_variant	Intron 5 of 6	ENST00000634734.3	NP_004314.6
BAG1	NM_001349286.2	c.673-254A>C		intron_variant	Intron 5 of 6		NP_001336215.1
BAG1	NM_001172415.2	c.541-254A>C		intron_variant	Intron 5 of 6		NP_001165886.1
BAG1	NM_001349299.2	c.472-254A>C		intron_variant	Intron 5 of 6		NP_001336228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG1	ENST00000634734.3	c.886-254A>C		intron_variant	Intron 5 of 6	1	NM_004323.6	ENSP00000489189.2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58039 AN: 151954 Hom.: 14990 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.0947

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.382 AC: 58134 AN: 152074 Hom.: 15027 Cov.: 32 AF XY: 0.376 AC XY: 27959 AN XY: 74374

African (AFR) AF: 0.744 AC: 30834 AN: 41448

American (AMR) AF: 0.304 AC: 4650 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1337 AN: 5174

South Asian (SAS) AF: 0.282 AC: 1358 AN: 4816

European-Finnish (FIN) AF: 0.221 AC: 2340 AN: 10592

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15830 AN: 67980

Other (OTH) AF: 0.353 AC: 746 AN: 2112

Alfa AF: 0.286 Hom.: 9836

Bravo AF: 0.404

Asia WGS AF: 0.339 AC: 1179 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	5.7
DANN	Benign	0.71
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs706118; hg19: chr9-33256179;