chr18-63311780-G-A

Position:

• chr18-63311780-G-A

Variant summary

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

The NM_000633.3(BCL2):​c.585+6302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,908 control chromosomes in the GnomAD database, including 14,536 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 0.44 (14536 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.585+6302C>T		intron_variant		ENST00000333681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.585+6302C>T		intron_variant		1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66212 AN: 151792 Hom.: 14537 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.436 AC: 66227 AN: 151908 Hom.: 14536 Cov.: 32 AF XY: 0.433 AC XY: 32127 AN XY: 74262

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.419

Alfa AF: 0.431 Hom.: 14880

Bravo AF: 0.433

Asia WGS AF: 0.377 AC: 1310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0070
DANN	Benign	0.68

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: rs949037; hg19: chr18-60979013;