chr18-63268814-A-G

Variant names:

• chr18-63268814-A-G
• rs8094315
• NM_000633.3:c.585+49268T>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+49268T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,156 control chromosomes in the GnomAD database, including 2,982 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 0.18 (2982 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771
• Publications: 13 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+49268T>C		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+49268T>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+49268T>C		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27393 AN: 152038 Hom.: 2981 Cov.: 32

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.180 AC: 27392 AN: 152156 Hom.: 2982 Cov.: 32 AF XY: 0.182 AC XY: 13525 AN XY: 74374

African (AFR) AF: 0.0775 AC: 3221 AN: 41536

American (AMR) AF: 0.148 AC: 2257 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2017 AN: 5172

South Asian (SAS) AF: 0.319 AC: 1534 AN: 4814

European-Finnish (FIN) AF: 0.231 AC: 2441 AN: 10554

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14762 AN: 68008

Other (OTH) AF: 0.165 AC: 348 AN: 2112

Alfa AF: 0.201 Hom.: 14772

Bravo AF: 0.167

Asia WGS AF: 0.310 AC: 1075 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.043
DANN	Benign	0.87
PhyloP100		-0.77
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: rs8094315; hg19: chr18-60936047;