18-63319604-G-T

Variant names:

• chr18-63319604-G-T
• rs2279115
• NM_000633.3:c.-717C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000633.3(BCL2):​c.-717C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 225,270 control chromosomes in the GnomAD database, including 25,508 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 0.44 (16590 hom., cov: 32)
  • Exomes 𝑓: 0.48 (8918 hom.)
• Consequence: BCL2 NM_000633.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 132 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 (AMR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	NM_000633.3	MANE Select	c.-717C>A		5_prime_UTR	Exon 1 of 3	NP_000624.2
	BCL2	NM_000657.3		c.-717C>A		5_prime_UTR	Exon 1 of 2	NP_000648.2
	BCL2	NM_001438935.1		c.-717C>A		5_prime_UTR	Exon 1 of 3	NP_001425864.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	ENST00000333681.5	TSL:1 MANE Select	c.-717C>A		5_prime_UTR	Exon 1 of 3	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.-938C>A		5_prime_UTR	Exon 1 of 2	ENSP00000381185.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67461 AN: 151906 Hom.: 16583 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.484 AC: 35476 AN: 73246 Hom.: 8918 Cov.: 0 AF XY: 0.486 AC XY: 16449 AN XY: 33838

African (AFR) AF: 0.226 AC: 764 AN: 3378

American (AMR) AF: 0.605 AC: 1344 AN: 2220

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1926 AN: 4608

East Asian (EAS) AF: 0.374 AC: 3967 AN: 10600

South Asian (SAS) AF: 0.340 AC: 215 AN: 632

European-Finnish (FIN) AF: 0.550 AC: 33 AN: 60

Middle Eastern (MID) AF: 0.516 AC: 225 AN: 436

European-Non Finnish (NFE) AF: 0.533 AC: 24078 AN: 45188

Other (OTH) AF: 0.477 AC: 2924 AN: 6124

GnomAD4 genome AF: 0.444 AC: 67495 AN: 152024 Hom.: 16590 Cov.: 32 AF XY: 0.445 AC XY: 33110 AN XY: 74326

African (AFR) AF: 0.223 AC: 9238 AN: 41490

American (AMR) AF: 0.566 AC: 8653 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1443 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2082 AN: 5168

South Asian (SAS) AF: 0.356 AC: 1713 AN: 4816

European-Finnish (FIN) AF: 0.544 AC: 5744 AN: 10554

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36877 AN: 67918

Other (OTH) AF: 0.482 AC: 1015 AN: 2106

Alfa AF: 0.500 Hom.: 7781

Bravo AF: 0.440

Asia WGS AF: 0.361 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.83
PhyloP100		1.3
Mutation Taster		=300/0	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: rs2279115; hg19: chr18-60986837;