rs2448050

Positions:

• chr12-12096290-G-A

Variant summary

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

The NM_138723.2(BCL2L14):​c.945+1360G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 522,798 control chromosomes in the GnomAD database, including 81,399 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 0.51 (20311 hom., cov: 31)
  • Exomes 𝑓: 0.57 (61088 hom.)
• Consequence: BCL2L14 NM_138723.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651

Genes affected

BCL2L14 (HGNC:16657): (BCL2 like 14) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Overexpression of this gene has been shown to induce apoptosis in cells. Three alternatively spliced transcript variants encoding two distinct isoforms have been reported for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L14	NM_138723.2	c.945+1360G>A		intron_variant		ENST00000308721.9	NP_620049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L14	ENST00000308721.9	c.945+1360G>A		intron_variant		1	NM_138723.2	ENSP00000309132.4

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77307 AN: 151654 Hom.: 20309 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.573 AC: 212714 AN: 371026 Hom.: 61088 AF XY: 0.573 AC XY: 100505 AN XY: 175278

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.643

Gnomad4 SAS exome AF: 0.577

Gnomad4 FIN exome AF: 0.524

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.568

GnomAD4 genome AF: 0.510 AC: 77336 AN: 151772 Hom.: 20311 Cov.: 31 AF XY: 0.509 AC XY: 37744 AN XY: 74176

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.495

Alfa AF: 0.553 Hom.: 47783

Bravo AF: 0.499

Asia WGS AF: 0.555 AC: 1930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.46
DANN	Benign	0.74

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: rs2448050; hg19: chr12-12249224;