rs3927911

Variant names:

• chr18-63266393-G-A
• rs3927911
• NM_000633.3:c.585+51689C>T

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+51689C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,050 control chromosomes in the GnomAD database, including 7,232 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 0.29 (7232 hom., cov: 29)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 6 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 = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+51689C>T		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+51689C>T		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+51689C>T		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43737 AN: 150932 Hom.: 7232 Cov.: 29

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.290 AC: 43732 AN: 151050 Hom.: 7232 Cov.: 29 AF XY: 0.293 AC XY: 21602 AN XY: 73674

African (AFR) AF: 0.116 AC: 4773 AN: 41152

American (AMR) AF: 0.337 AC: 5098 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1174 AN: 3466

East Asian (EAS) AF: 0.272 AC: 1391 AN: 5110

South Asian (SAS) AF: 0.329 AC: 1577 AN: 4796

European-Finnish (FIN) AF: 0.389 AC: 3990 AN: 10250

Middle Eastern (MID) AF: 0.410 AC: 119 AN: 290

European-Non Finnish (NFE) AF: 0.361 AC: 24521 AN: 67850

Other (OTH) AF: 0.316 AC: 663 AN: 2098

Alfa AF: 0.340 Hom.: 17081

Bravo AF: 0.275

Asia WGS AF: 0.290 AC: 1005 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.56
PhyloP100		0.63
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: rs3927911; hg19: chr18-60933626;