18-63311353-G-T

Position:

• chr18-63311353-G-T

Variant summary

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

The ENST00000333681.5(BCL2):​c.585+6729C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 152,084 control chromosomes in the GnomAD database, including 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 0.097 (866 hom., cov: 32)
• Consequence: BCL2 ENST00000333681.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+6729C>A		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+6729C>A		intron_variant		1	NM_000633.3	ENSP00000329623	P1

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14809 AN: 151966 Hom.: 864 Cov.: 32

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0632

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0938

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.0974 AC: 14820 AN: 152084 Hom.: 866 Cov.: 32 AF XY: 0.0993 AC XY: 7384 AN XY: 74348

Gnomad4 AFR AF: 0.0711

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.0632

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.0637

Gnomad4 FIN AF: 0.0789

Gnomad4 NFE AF: 0.0938

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0937 Hom.: 1144

Bravo AF: 0.105

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.66

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: rs12458289; hg19: chr18-60978586;