rs706115

Variant names:

• chr9-33253607-C-G
• rs706115
• NM_004323.6:c.*1612G>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.*1612G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,874 control chromosomes in the GnomAD database, including 3,093 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 0.19 (3093 hom., cov: 30)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: BAG1 NM_004323.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 9 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004323.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG1	NM_004323.6	MANE Select	c.*1612G>C		3_prime_UTR	Exon 7 of 7	NP_004314.6
	BAG1	NM_001349286.2		c.*1612G>C		3_prime_UTR	Exon 7 of 7	NP_001336215.1
	BAG1	NM_001172415.2		c.*1612G>C		3_prime_UTR	Exon 7 of 7	NP_001165886.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG1	ENST00000634734.3	TSL:1 MANE Select	c.*1612G>C		3_prime_UTR	Exon 7 of 7	ENSP00000489189.2
	BAG1	ENST00000493917.5	TSL:5	n.69+2258G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29372 AN: 151754 Hom.: 3088 Cov.: 30

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.194 AC: 29402 AN: 151870 Hom.: 3093 Cov.: 30 AF XY: 0.193 AC XY: 14357 AN XY: 74258

African (AFR) AF: 0.257 AC: 10626 AN: 41426

American (AMR) AF: 0.197 AC: 3014 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3466

East Asian (EAS) AF: 0.163 AC: 838 AN: 5152

South Asian (SAS) AF: 0.204 AC: 976 AN: 4790

European-Finnish (FIN) AF: 0.167 AC: 1755 AN: 10536

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11066 AN: 67920

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.189 Hom.: 380

Bravo AF: 0.196

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.69
PhyloP100		1.1
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

Other links and lift over

dbSNP: rs706115; hg19: chr9-33253605;