rs1381548

Positions:

• chr18-63290163-G-A
• chr18-63290163-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000633.3(BCL2):​c.585+27919C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,962 control chromosomes in the GnomAD database, including 10,987 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 0.38 (10987 hom., cov: 31)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+27919C>T		intron_variant		ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+27919C>T		intron_variant			XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.585+27919C>T		intron_variant		1	NM_000633.3	ENSP00000329623	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57141 AN: 151844 Hom.: 10975 Cov.: 31

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.376 AC: 57190 AN: 151962 Hom.: 10987 Cov.: 31 AF XY: 0.371 AC XY: 27582 AN XY: 74306

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.392

Alfa AF: 0.405 Hom.: 18255

Bravo AF: 0.379

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.38
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs1381548; hg19: chr18-60957396;