18-63313638-T-C

Position:

• chr18-63313638-T-C

Variant summary

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

The ENST00000333681.5(BCL2):​c.585+4444A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,016 control chromosomes in the GnomAD database, including 16,866 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 0.45 (16866 hom., cov: 32)
• Consequence: BCL2 ENST00000333681.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824

Genes affected

BCL2 (HGNC:990): (BCL2 apoptosis regulator) This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+4444A>G		intron_variant		ENST00000333681.5	NP_000624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.585+4444A>G		intron_variant		1	NM_000633.3	ENSP00000329623	P1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68135 AN: 151898 Hom.: 16854 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.448 AC: 68176 AN: 152016 Hom.: 16866 Cov.: 32 AF XY: 0.451 AC XY: 33509 AN XY: 74284

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.484

Alfa AF: 0.514 Hom.: 17442

Bravo AF: 0.443

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.31
DANN	Benign	0.58

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: rs1462129; hg19: chr18-60980871;