rs2304206

Variant names:

• chr19-49665614-G-A
• rs2304206
• ENST00000246785.7:c.-462G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-49665614-G-A
• chr19-49665614-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000246785.7(BCL2L12):​c.-462G>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 ENST00000246785.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 49 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.-9+17C>T		intron_variant	Intron 1 of 7	ENST00000377139.8	NP_001562.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54731 AN: 151714 Hom.: 11832 Cov.: 32

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.: 6 AF XY: 0.272 AC XY: 64101 AN XY: 235596

African (AFR) AF: 0.623 AC: 7867 AN: 12636

American (AMR) AF: 0.307 AC: 5398 AN: 17580

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 3202 AN: 13034

East Asian (EAS) AF: 0.188 AC: 5489 AN: 29274

South Asian (SAS) AF: 0.316 AC: 13191 AN: 41784

European-Finnish (FIN) AF: 0.230 AC: 6213 AN: 26960

Middle Eastern (MID) AF: 0.395 AC: 730 AN: 1850

European-Non Finnish (NFE) AF: 0.258 AC: 73377 AN: 284716

Other (OTH) AF: 0.288 AC: 7278 AN: 25290

GnomAD4 genome AF: 0.361 AC: 54820 AN: 151830 Hom.: 11867 Cov.: 32 AF XY: 0.355 AC XY: 26329 AN XY: 74198

African (AFR) AF: 0.617 AC: 25519 AN: 41362

American (AMR) AF: 0.321 AC: 4901 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3470

East Asian (EAS) AF: 0.188 AC: 969 AN: 5160

South Asian (SAS) AF: 0.306 AC: 1471 AN: 4812

European-Finnish (FIN) AF: 0.224 AC: 2356 AN: 10518

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17652 AN: 67946

Other (OTH) AF: 0.327 AC: 686 AN: 2096

Alfa AF: 0.276 Hom.: 16071

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
PhyloP100		-0.33
PromoterAI		-0.0029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2304206; hg19: chr19-50168871; COSMIC: COSV107206570; COSMIC: COSV107206570;