rs885720

Positions:

• chr12-12095165-A-G
• chr12-12095165-A-T

Variant summary

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

The NM_138723.2(BCL2L14):​c.945+235A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 984,812 control chromosomes in the GnomAD database, including 310,523 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 0.71 (39801 hom., cov: 30)
  • Exomes 𝑓: 0.80 (270722 hom.)
• Consequence: BCL2L14 NM_138723.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.93

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L14	NM_138723.2	c.945+235A>G		intron_variant		ENST00000308721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2L14	ENST00000308721.9	c.945+235A>G		intron_variant		1	NM_138723.2	P1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108147 AN: 151770 Hom.: 39775 Cov.: 30

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.743

GnomAD4 exome AF: 0.805 AC: 670268 AN: 832926 Hom.: 270722 Cov.: 35 AF XY: 0.805 AC XY: 309595 AN XY: 384634

Gnomad4 AFR exome AF: 0.498

Gnomad4 AMR exome AF: 0.660

Gnomad4 ASJ exome AF: 0.819

Gnomad4 EAS exome AF: 0.649

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.808

Gnomad4 NFE exome AF: 0.814

Gnomad4 OTH exome AF: 0.790

GnomAD4 genome AF: 0.712 AC: 108217 AN: 151886 Hom.: 39801 Cov.: 30 AF XY: 0.713 AC XY: 52935 AN XY: 74230

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.739

Alfa AF: 0.792 Hom.: 63040

Bravo AF: 0.694

Asia WGS AF: 0.669 AC: 2327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.21
DANN	Benign	0.77

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: rs885720; hg19: chr12-12248099;