18-63319604-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000633.3(BCL2):​c.-717C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BCL2 NM_000633.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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>G		5_prime_UTR	Exon 1 of 3	NP_000624.2
	BCL2	NM_000657.3		c.-717C>G		5_prime_UTR	Exon 1 of 2	NP_000648.2
	BCL2	NM_001438935.1		c.-717C>G		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>G		5_prime_UTR	Exon 1 of 3	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.-938C>G		5_prime_UTR	Exon 1 of 2	ENSP00000381185.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 73428 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 33920

African (AFR) AF: 0.00 AC: 0 AN: 3384

American (AMR) AF: 0.00 AC: 0 AN: 2224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4618

East Asian (EAS) AF: 0.00 AC: 0 AN: 10610

South Asian (SAS) AF: 0.00 AC: 0 AN: 636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 60

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 438

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 45302

Other (OTH) AF: 0.00 AC: 0 AN: 6156

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.74
PhyloP100		1.3
PromoterAI		0.0097	Neutral

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;