rs10845472

Variant names:

• chr12-12085221-G-C
• rs10845472
• NM_138723.2:c.434-1992G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138723.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L14	NM_138723.2	MANE Select	c.434-1992G>C		intron	N/A	NP_620049.1
	BCL2L14	NM_001370268.1		c.434-1992G>C		intron	N/A	NP_001357197.1
	BCL2L14	NM_001370269.1		c.434-1992G>C		intron	N/A	NP_001357198.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L14	ENST00000308721.9	TSL:1 MANE Select	c.434-1992G>C		intron	N/A	ENSP00000309132.4
	BCL2L14	ENST00000396367.5	TSL:1	c.434-1992G>C		intron	N/A	ENSP00000379653.1
	BCL2L14	ENST00000266434.8	TSL:1	c.434-1992G>C		intron	N/A	ENSP00000266434.4

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

African (AFR) AF: 0.235 AC: 9764 AN: 41498

American (AMR) AF: 0.236 AC: 3603 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1111 AN: 3466

East Asian (EAS) AF: 0.126 AC: 650 AN: 5162

South Asian (SAS) AF: 0.130 AC: 625 AN: 4824

European-Finnish (FIN) AF: 0.344 AC: 3637 AN: 10576

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19553 AN: 67994

Other (OTH) AF: 0.284 AC: 599 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.4
DANN	Benign	0.35
PhyloP100		-0.25
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: rs10845472; hg19: chr12-12238155;