rs10845472

Positions:

• chr12-12085221-G-C

Variant summary

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

The NM_138723.2(BCL2L14):​c.434-1992G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,118 control chromosomes in the GnomAD database, including 5,471 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 0.26 (5471 hom., cov: 32)
• Consequence: BCL2L14 NM_138723.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L14	NM_138723.2	c.434-1992G>C		intron_variant		ENST00000308721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2L14	ENST00000308721.9	c.434-1992G>C		intron_variant		1	NM_138723.2	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39829 AN: 151998 Hom.: 5455 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.286

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 39886 AN: 152118 Hom.: 5471 Cov.: 32 AF XY: 0.262 AC XY: 19456 AN XY: 74342

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.284

Alfa AF: 0.276 Hom.: 728

Bravo AF: 0.254

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.4
DANN	Benign	0.35

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: rs10845472; hg19: chr12-12238155;