18-63142550-A-G

Variant names:

• chr18-63142550-A-G
• rs17756073
• NM_000633.3:c.586-13791T>C

Variant summary

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

The NM_000633.3(BCL2):​c.586-13791T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,082 control chromosomes in the GnomAD database, including 5,103 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 0.25 (5103 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.660

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-13791T>C		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-13791T>C		intron_variant	Intron 1 of 1		XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.586-13791T>C		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37833 AN: 151964 Hom.: 5108 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.249 AC: 37823 AN: 152082 Hom.: 5103 Cov.: 32 AF XY: 0.244 AC XY: 18176 AN XY: 74348

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.253

Alfa AF: 0.294 Hom.: 11550

Bravo AF: 0.241

Asia WGS AF: 0.201 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.56

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: rs17756073; hg19: chr18-60809783;