20-31674356-C-T

Variant names:

• chr20-31674356-C-T
• rs6060627
• NM_138578.3:c.565-8270G>A

Variant summary

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

The NM_138578.3(BCL2L1):​c.565-8270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,024 control chromosomes in the GnomAD database, including 15,399 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 0.40 (15399 hom., cov: 31)
• Consequence: BCL2L1 NM_138578.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.63
• Publications: 22 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]

LOC124904883 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L1	NM_138578.3	c.565-8270G>A		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.565-8270G>A		intron_variant	Intron 2 of 2	1	NM_138578.3	ENSP00000302564.4

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60941 AN: 151906 Hom.: 15362 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.401 AC: 61030 AN: 152024 Hom.: 15399 Cov.: 31 AF XY: 0.395 AC XY: 29376 AN XY: 74292

African (AFR) AF: 0.710 AC: 29409 AN: 41446

American (AMR) AF: 0.281 AC: 4290 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3468

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5186

South Asian (SAS) AF: 0.101 AC: 488 AN: 4820

European-Finnish (FIN) AF: 0.394 AC: 4155 AN: 10540

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20417 AN: 67968

Other (OTH) AF: 0.374 AC: 789 AN: 2112

Alfa AF: 0.289 Hom.: 4151

Bravo AF: 0.412

Asia WGS AF: 0.101 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.37
PhyloP100		-3.6
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: rs6060627; hg19: chr20-30262159;