1-234605171-C-CAGTTATAAT

Variant names:

• chr1-234605171-C-CAGTTATAAT
• rs3045215
• NM_182972.3:c.*1965_*1966insATTATAACT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_182972.3(IRF2BP2):​c.*1965_*1966insATTATAACT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (40922 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: IRF2BP2 NM_182972.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02
• Publications: 10 publications found

Genes affected

IRF2BP2 (HGNC:21729): (interferon regulatory factor 2 binding protein 2) This gene encodes an interferon regulatory factor-2 (IRF2) binding protein that interacts with the C-terminal transcriptional repression domain of IRF2. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

IRF2BP2 Gene-Disease associations (from GenCC):

• immunodeficiency, common variable, 14

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BP2	NM_182972.3	c.*1965_*1966insATTATAACT		3_prime_UTR_variant	Exon 2 of 2	ENST00000366609.4	NP_892017.2
IRF2BP2	NM_001077397.1	c.*1965_*1966insATTATAACT		3_prime_UTR_variant	Exon 2 of 2		NP_001070865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BP2	ENST00000366609.4	c.*1965_*1966insATTATAACT		3_prime_UTR_variant	Exon 2 of 2	1	NM_182972.3	ENSP00000355568.3
IRF2BP2	ENST00000366610.8	c.*1965_*1966insATTATAACT		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000355569.3

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109687 AN: 151546 Hom.: 40877 Cov.: 0

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.728

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.724 AC: 109784 AN: 151664 Hom.: 40922 Cov.: 0 AF XY: 0.713 AC XY: 52892 AN XY: 74132

African (AFR) AF: 0.841 AC: 34779 AN: 41378

American (AMR) AF: 0.619 AC: 9449 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2564 AN: 3466

East Asian (EAS) AF: 0.263 AC: 1360 AN: 5166

South Asian (SAS) AF: 0.461 AC: 2223 AN: 4820

European-Finnish (FIN) AF: 0.713 AC: 7510 AN: 10530

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49568 AN: 67732

Other (OTH) AF: 0.725 AC: 1525 AN: 2104

Alfa AF: 0.599 Hom.: 1152

Bravo AF: 0.722

Asia WGS AF: 0.426 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3045215; hg19: chr1-234740917; COSMIC: COSV64014684; COSMIC: COSV64014684;