20-31688103-A-G

Variant names:

• chr20-31688103-A-G
• rs6058381
• NM_138578.3:c.565-22017T>C

Variant summary

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

The ENST00000307677.5(BCL2L1):​c.565-22017T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0772 in 152,202 control chromosomes in the GnomAD database, including 463 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 0.077 (463 hom., cov: 30)
• Consequence: BCL2L1 ENST00000307677.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 9 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000307677.5. 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
	BCL2L1	NM_138578.3	MANE Select	c.565-22017T>C		intron	N/A	NP_612815.1
	BCL2L1	NM_001317919.2		c.565-22017T>C		intron	N/A	NP_001304848.1
	BCL2L1	NM_001317920.2		c.565-22017T>C		intron	N/A	NP_001304849.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L1	ENST00000307677.5	TSL:1 MANE Select	c.565-22017T>C		intron	N/A	ENSP00000302564.4
	BCL2L1	ENST00000376062.6	TSL:1	c.565-22017T>C		intron	N/A	ENSP00000365230.2
	BCL2L1	ENST00000450273.2	TSL:3	c.565-3515T>C		intron	N/A	ENSP00000406203.2

Frequencies

GnomAD3 genomes AF: 0.0771 AC: 11729 AN: 152084 Hom.: 460 Cov.: 30

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0579

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.0869

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

GnomAD4 genome AF: 0.0772 AC: 11757 AN: 152202 Hom.: 463 Cov.: 30 AF XY: 0.0746 AC XY: 5555 AN XY: 74436

African (AFR) AF: 0.101 AC: 4199 AN: 41512

American (AMR) AF: 0.0578 AC: 884 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 296 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0265 AC: 128 AN: 4828

European-Finnish (FIN) AF: 0.0726 AC: 770 AN: 10610

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0763 AC: 5186 AN: 68006

Other (OTH) AF: 0.0864 AC: 182 AN: 2106

Alfa AF: 0.0772 Hom.: 816

Bravo AF: 0.0781

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.18
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: rs6058381; hg19: chr20-30275906;