chr19-49673914-G-A

Position:

• chr19-49673914-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138639.2(BCL2L12):​c.*166G>A variant causes a 3 prime UTR 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. 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 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L12	NM_138639.2	c.*166G>A		3_prime_UTR_variant	7/7	ENST00000246784.8	NP_619580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L12	ENST00000246784.8	c.*166G>A		3_prime_UTR_variant	7/7	1	NM_138639.2	ENSP00000246784	P4

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

Gnomad4 AFR exome AF: 0.0191

Gnomad4 AMR exome AF: 0.0560

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.0750

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.0692

Gnomad4 NFE exome AF: 0.0969

Gnomad4 OTH exome AF: 0.0957

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

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.0652

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0847

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.0535

Gnomad4 NFE AF: 0.0980

Gnomad4 OTH AF: 0.0853

Alfa AF: 0.0940 Hom.: 1123

Bravo AF: 0.0670

Asia WGS AF: 0.169 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.48
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs3745469; hg19: chr19-50177171;