rs1800477

Variant names:

• chr18-63318540-C-A
• rs1800477
• NM_000633.3:c.127G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-63318540-C-A
• chr18-63318540-C-G
• chr18-63318540-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000633.3(BCL2):​c.127G>T​(p.Ala43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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: 7.0e-7 (0 hom.)
• Consequence: BCL2 NM_000633.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079901904).

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.127G>T	p.Ala43Ser	missense	Exon 2 of 3	NP_000624.2	P10415-1
	BCL2	NM_000657.3		c.127G>T	p.Ala43Ser	missense	Exon 2 of 2	NP_000648.2	P10415-2
	BCL2	NM_001438935.1		c.127G>T	p.Ala43Ser	missense	Exon 2 of 3	NP_001425864.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	ENST00000333681.5	TSL:1 MANE Select	c.127G>T	p.Ala43Ser	missense	Exon 2 of 3	ENSP00000329623.3	P10415-1
	BCL2	ENST00000398117.1	TSL:1	c.127G>T	p.Ala43Ser	missense	Exon 1 of 2	ENSP00000381185.1	P10415-1
	BCL2	ENST00000589955.2	TSL:6	c.127G>T	p.Ala43Ser	missense	Exon 1 of 1	ENSP00000466417.1	P10415-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432368 Hom.: 0 Cov.: 34 AF XY: 0.00000140 AC XY: 1 AN XY: 712886

African (AFR) AF: 0.00 AC: 0 AN: 30674

American (AMR) AF: 0.00 AC: 0 AN: 41360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25226

East Asian (EAS) AF: 0.00 AC: 0 AN: 36528

South Asian (SAS) AF: 0.00 AC: 0 AN: 84788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101256

Other (OTH) AF: 0.0000169 AC: 1 AN: 59212

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.9
DANN	Benign	0.78
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.025
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.035
Sift	Benign	0.66	T
Sift4G	Benign	0.54	T
Polyphen		0.99	D
Vest4		0.063
MutPred		0.14		Gain of glycosylation at A43 (P = 0.01)
MVP		0.45
MPC		0.81
ClinPred		0.14	T
GERP RS		1.6
PromoterAI		0.050	Neutral
Varity_R		0.035
gMVP		0.33
Mutation Taster		=97/3	polymorphism

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: rs1800477; hg19: chr18-60985773;