rs1994251

Positions:

• chr20-31699525-T-G

Variant summary

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

The NM_138578.3(BCL2L1):​c.564+22130A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,176 control chromosomes in the GnomAD database, including 8,257 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 0.29 (8257 hom., cov: 33)
• Consequence: BCL2L1 NM_138578.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648

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:40095): (BCL2L1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L1	NM_138578.3	c.564+22130A>C		intron_variant		ENST00000307677.5
BCL2L1-AS1	XR_007067558.1	n.11277+13141T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2L1	ENST00000307677.5	c.564+22130A>C		intron_variant		1	NM_138578.3	P1
BCL2L1-AS1	ENST00000412972.1	n.169+13141T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44580 AN: 152058 Hom.: 8251 Cov.: 33

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.293 AC: 44615 AN: 152176 Hom.: 8257 Cov.: 33 AF XY: 0.290 AC XY: 21609 AN XY: 74388

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0634

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.259

Alfa AF: 0.272 Hom.: 835

Bravo AF: 0.299

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.64

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: rs1994251; hg19: chr20-30287328;