18-63304411-A-T

Position:

• chr18-63304411-A-T

Variant summary

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

The NM_000633.3(BCL2):​c.585+13671T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,236 control chromosomes in the GnomAD database, including 899 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 0.10 (899 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+13671T>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+13671T>A		intron_variant		1	NM_000633.3	ENSP00000329623	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15687 AN: 152118 Hom.: 898 Cov.: 32

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0799

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.103 AC: 15694 AN: 152236 Hom.: 899 Cov.: 32 AF XY: 0.104 AC XY: 7736 AN XY: 74420

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0799

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.0617

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0443 Hom.: 33

Bravo AF: 0.104

Asia WGS AF: 0.103 AC: 358 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.49

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: rs2849377; hg19: chr18-60971644;