rs8089538

Variant names:

• chr18-63276318-A-G
• rs8089538
• NM_000633.3:c.585+41764T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000633.3(BCL2):​c.585+41764T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,060 control chromosomes in the GnomAD database, including 9,471 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 0.35 (9471 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+41764T>C		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+41764T>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.585+41764T>C		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52514 AN: 151942 Hom.: 9477 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.345 AC: 52509 AN: 152060 Hom.: 9471 Cov.: 32 AF XY: 0.344 AC XY: 25556 AN XY: 74334

African (AFR) AF: 0.252 AC: 10429 AN: 41432

American (AMR) AF: 0.335 AC: 5124 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1178 AN: 3472

East Asian (EAS) AF: 0.240 AC: 1242 AN: 5178

South Asian (SAS) AF: 0.345 AC: 1660 AN: 4814

European-Finnish (FIN) AF: 0.405 AC: 4286 AN: 10580

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27258 AN: 67972

Other (OTH) AF: 0.363 AC: 767 AN: 2114

Alfa AF: 0.381 Hom.: 14532

Bravo AF: 0.333

Asia WGS AF: 0.293 AC: 1018 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.78
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8089538; hg19: chr18-60943551;