rs1994251

Variant names:

• chr20-31699525-T-G
• rs1994251
• NM_138578.3:c.564+22130A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BCL2L1	NM_138578.3	c.564+22130A>C		intron_variant	Intron 2 of 2	ENST00000307677.5	NP_612815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L1	ENST00000307677.5	c.564+22130A>C		intron_variant	Intron 2 of 2	1	NM_138578.3	ENSP00000302564.4

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

African (AFR) AF: 0.514 AC: 21338 AN: 41516

American (AMR) AF: 0.208 AC: 3183 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3466

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0634 AC: 306 AN: 4830

European-Finnish (FIN) AF: 0.319 AC: 3377 AN: 10578

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14869 AN: 68002

Other (OTH) AF: 0.259 AC: 548 AN: 2112

Alfa AF: 0.281 Hom.: 936

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
PhyloP100		0.65
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: rs1994251; hg19: chr20-30287328;