rs1484994

Positions:

• chr20-31718172-A-G
• chr20-31718172-A-T

Variant summary

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

The NM_138578.3(BCL2L1):​c.564+3483T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,056 control chromosomes in the GnomAD database, including 12,436 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 0.37 (12436 hom., cov: 32)
• Consequence: BCL2L1 NM_138578.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

Genes affected

BCL2L1 (HGNC:992): (BCL2 like 1) The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The proteins encoded by this gene are located at the outer mitochondrial membrane, and have been shown to regulate outer mitochondrial membrane channel (VDAC) opening. VDAC regulates mitochondrial membrane potential, and thus controls the production of reactive oxygen species and release of cytochrome C by mitochondria, both of which are the potent inducers of cell apoptosis. Alternative splicing results in multiple transcript variants encoding two different isoforms. The longer isoform acts as an apoptotic inhibitor and the shorter isoform acts as an apoptotic activator. [provided by RefSeq, Dec 2015]

BCL2L1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L1	NM_138578.3	c.564+3483T>C		intron_variant		ENST00000307677.5
BCL2L1-AS1	XR_007067558.1	n.12829A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2L1	ENST00000307677.5	c.564+3483T>C		intron_variant		1	NM_138578.3	P1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56006 AN: 151936 Hom.: 12414 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0895

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.369 AC: 56074 AN: 152056 Hom.: 12436 Cov.: 32 AF XY: 0.364 AC XY: 27013 AN XY: 74312

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0898

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.346

Alfa AF: 0.299 Hom.: 12109

Bravo AF: 0.375

Asia WGS AF: 0.0800 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.9
DANN	Benign	0.61

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: rs1484994; hg19: chr20-30305975;