NM_000633.3:c.585+81337G>C

Variant names:

• chr18-63236745-C-G
• rs3810027
• NM_000633.3:c.585+81337G>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+81337G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,002 control chromosomes in the GnomAD database, including 10,579 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 0.37 (10579 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+81337G>C		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+81337G>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+81337G>C		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56389 AN: 151884 Hom.: 10562 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.371 AC: 56442 AN: 152002 Hom.: 10579 Cov.: 32 AF XY: 0.376 AC XY: 27915 AN XY: 74310

African (AFR) AF: 0.416 AC: 17232 AN: 41466

American (AMR) AF: 0.386 AC: 5893 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1108 AN: 3468

East Asian (EAS) AF: 0.408 AC: 2107 AN: 5170

South Asian (SAS) AF: 0.444 AC: 2135 AN: 4810

European-Finnish (FIN) AF: 0.377 AC: 3981 AN: 10552

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22810 AN: 67958

Other (OTH) AF: 0.392 AC: 824 AN: 2104

Alfa AF: 0.199 Hom.: 410

Bravo AF: 0.372

Asia WGS AF: 0.420 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.058
DANN	Benign	0.68
PhyloP100		-1.5
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: rs3810027; hg19: chr18-60903978;