18-63304411-A-T

Variant names:

• chr18-63304411-A-T
• rs2849377
• NM_000633.3:c.585+13671T>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.585+13671T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,236 control chromosomes in the GnomAD database, including 899 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 0.10 (899 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.134 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	NM_000633.3	MANE Select	c.585+13671T>A		intron	N/A	NP_000624.2	P10415-1
	BCL2	NM_001438935.1		c.586-2546T>A		intron	N/A	NP_001425864.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	ENST00000333681.5	TSL:1 MANE Select	c.585+13671T>A		intron	N/A	ENSP00000329623.3	P10415-1
	BCL2	ENST00000398117.1	TSL:1	c.585+13671T>A		intron	N/A	ENSP00000381185.1	P10415-1
	BCL2	ENST00000677227.1		n.585+13671T>A		intron	N/A	ENSP00000504566.1	A0A7I2V5Q7

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15687 AN: 152118 Hom.: 898 Cov.: 32

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0799

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.103 AC: 15694 AN: 152236 Hom.: 899 Cov.: 32 AF XY: 0.104 AC XY: 7736 AN XY: 74420

African (AFR) AF: 0.0645 AC: 2682 AN: 41550

American (AMR) AF: 0.139 AC: 2127 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0799 AC: 277 AN: 3468

East Asian (EAS) AF: 0.127 AC: 656 AN: 5180

South Asian (SAS) AF: 0.0617 AC: 298 AN: 4826

European-Finnish (FIN) AF: 0.118 AC: 1252 AN: 10606

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7939 AN: 67998

Other (OTH) AF: 0.109 AC: 230 AN: 2114

Alfa AF: 0.0443 Hom.: 33

Bravo AF: 0.104

Asia WGS AF: 0.103 AC: 358 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		0.091
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: rs2849377; hg19: chr18-60971644;