rs1893506

Variant names:

• chr18-63226447-A-G
• rs1893506
• NM_000633.3:c.585+91635T>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+91635T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 152,236 control chromosomes in the GnomAD database, including 573 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 0.085 (573 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• 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]

ENSG00000308299 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+91635T>C		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+91635T>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+91635T>C		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12874 AN: 152118 Hom.: 569 Cov.: 32

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.0812

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

GnomAD4 genome AF: 0.0847 AC: 12899 AN: 152236 Hom.: 573 Cov.: 32 AF XY: 0.0872 AC XY: 6487 AN XY: 74426

African (AFR) AF: 0.0964 AC: 4002 AN: 41536

American (AMR) AF: 0.0870 AC: 1331 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3468

East Asian (EAS) AF: 0.114 AC: 589 AN: 5184

South Asian (SAS) AF: 0.162 AC: 781 AN: 4822

European-Finnish (FIN) AF: 0.0934 AC: 990 AN: 10598

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0689 AC: 4683 AN: 68012

Other (OTH) AF: 0.0855 AC: 181 AN: 2116

Alfa AF: 0.0738 Hom.: 174

Bravo AF: 0.0840

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.96
PhyloP100		0.32
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: rs1893506; hg19: chr18-60893680;