rs3745469

Variant names:

• chr19-49673914-G-A
• rs3745469
• NM_138639.2:c.*166G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-49673914-G-A
• chr19-49673914-G-C
• chr19-49673914-G-T

Variant summary

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

The NM_138639.2(BCL2L12):​c.*166G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 686,808 control chromosomes in the GnomAD database, including 3,387 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.072 (517 hom., cov: 32)
  • Exomes 𝑓: 0.097 (2870 hom.)
• Consequence: BCL2L12 NM_138639.2 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 20 publications found

Genes affected

BCL2L12 (HGNC:13787): (BCL2 like 12) This gene encodes a member of a family of proteins containing a Bcl-2 homology domain 2 (BH2). The encoded protein is an anti-apoptotic factor that acts as an inhibitor of caspases 3 and 7 in the cytoplasm. In the nucleus, it binds to the p53 tumor suppressor protein, preventing its association with target genes. Overexpression of this gene has been detected in a number of different cancers. There is a pseudogene for this gene on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138639.2. 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
	BCL2L12	NM_138639.2	MANE Select	c.*166G>A		splice_region	Exon 7 of 7	NP_619580.2	Q9HB09-1
	BCL2L12	NM_138639.2	MANE Select	c.*166G>A		3_prime_UTR	Exon 7 of 7	NP_619580.2	Q9HB09-1
	BCL2L12	NM_001040668.2		c.*166G>A		splice_region	Exon 7 of 7	NP_001035758.2	Q9HB09-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L12	ENST00000246784.8	TSL:1 MANE Select	c.*166G>A		splice_region	Exon 7 of 7	ENSP00000246784.4	Q9HB09-1
	BCL2L12	ENST00000246785.7	TSL:1	c.*166G>A		splice_region	Exon 7 of 7	ENSP00000246785.3	Q9HB09-1
	BCL2L12	ENST00000619007.4	TSL:1	c.*137G>A		splice_region	Exon 6 of 6	ENSP00000483272.2	A0A0X8AT42

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10959 AN: 152160 Hom.: 518 Cov.: 32

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0850

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.0833

GnomAD4 exome AF: 0.0968 AC: 51725 AN: 534530 Hom.: 2870 Cov.: 7 AF XY: 0.100 AC XY: 27487 AN XY: 274868

African (AFR) AF: 0.0191 AC: 270 AN: 14172

American (AMR) AF: 0.0560 AC: 1023 AN: 18278

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 1461 AN: 13504

East Asian (EAS) AF: 0.0750 AC: 2243 AN: 29916

South Asian (SAS) AF: 0.169 AC: 6682 AN: 39570

European-Finnish (FIN) AF: 0.0692 AC: 2214 AN: 31990

Middle Eastern (MID) AF: 0.198 AC: 697 AN: 3512

European-Non Finnish (NFE) AF: 0.0969 AC: 34503 AN: 356074

Other (OTH) AF: 0.0957 AC: 2632 AN: 27514

GnomAD4 genome AF: 0.0720 AC: 10959 AN: 152278 Hom.: 517 Cov.: 32 AF XY: 0.0726 AC XY: 5406 AN XY: 74446

African (AFR) AF: 0.0190 AC: 791 AN: 41562

American (AMR) AF: 0.0652 AC: 997 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 366 AN: 3472

East Asian (EAS) AF: 0.0847 AC: 439 AN: 5186

South Asian (SAS) AF: 0.165 AC: 794 AN: 4826

European-Finnish (FIN) AF: 0.0535 AC: 568 AN: 10608

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0980 AC: 6663 AN: 68024

Other (OTH) AF: 0.0853 AC: 180 AN: 2110

Alfa AF: 0.0895 Hom.: 2366

Bravo AF: 0.0670

Asia WGS AF: 0.169 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.48
DANN	Benign	0.51
PhyloP100		-0.27
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: rs3745469; hg19: chr19-50177171; COSMIC: COSV107206571; COSMIC: COSV107206571;