rs7236090

Positions:

• chr18-63279878-T-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+38204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,072 control chromosomes in the GnomAD database, including 15,622 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 0.42 (15622 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+38204A>G		intron_variant		ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+38204A>G		intron_variant			XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.585+38204A>G		intron_variant		1	NM_000633.3	ENSP00000329623	P1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63180 AN: 151954 Hom.: 15624 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.416 AC: 63188 AN: 152072 Hom.: 15622 Cov.: 32 AF XY: 0.414 AC XY: 30755 AN XY: 74304

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.467

Alfa AF: 0.537 Hom.: 30786

Bravo AF: 0.398

Asia WGS AF: 0.455 AC: 1580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.77

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: rs7236090; hg19: chr18-60947111;