dbSNP rs2304206: BCL2L12:c.-462G>A (chr19-49665614-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001282520.1(BCL2L12):c.-210G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 604,954 control chromosomes in the GnomAD database, including 29,952 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 0.36 ( 11867 hom., cov: 32)

Exomes 𝑓: 0.27 ( 18085 hom. )

Consequence

BCL2L12
NM_001282520.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.330

Variant links:

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]

BCL2L12 links:

IRF3 (HGNC:6118): (interferon regulatory factor 3) This gene encodes a member of the interferon regulatory transcription factor (IRF) family. The encoded protein is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP. This complex translocates to the nucleus and activates the transcription of interferons alpha and beta, as well as other interferon-induced genes. The protein plays an important role in the innate immune response against DNA and RNA viruses. Mutations in this gene are associated with Encephalopathy, acute, infection-induced, herpes-specific, 7. [provided by RefSeq, Sep 2020]

IRF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF3	NM_001571.6 link	c.-9+17C>T		intron_variant	Intron 1 of 7	ENST00000377139.8	NP_001562.1	Q14653-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF3	ENST00000377139.8 link	c.-9+17C>T		intron_variant	Intron 1 of 7	1	NM_001571.6	ENSP00000366344.3		Q14653-1

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54731

AN:

151714

Hom.:

11832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.326

GnomAD4 exome

AF:

0.271

AC:

122745

AN:

453124

Hom.:

18085

Cov.:

AF XY:

0.272

AC XY:

64101

AN XY:

235596

show subpopulations

Gnomad4 AFR exome

AF:

0.623

Gnomad4 AMR exome

AF:

0.307

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.316

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.361

AC:

54820

AN:

151830

Hom.:

11867

Cov.:

AF XY:

0.355

AC XY:

26329

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.617

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.327

Alfa

AF:

0.264

Hom.:

9413

Bravo

AF:

0.378

Asia WGS

AF:

0.344

AC:

1191

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

4.4

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over