1-234608667-C-T

Variant names:

• chr1-234608667-C-T
• rs4636
• NM_182972.3:c.828G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_182972.3(IRF2BP2):​c.828G>A​(p.Ala276Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,370,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A276A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: IRF2BP2 NM_182972.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 12 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)

ENSG00000228830 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.425 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BP2	NM_182972.3	c.828G>A	p.Ala276Ala	synonymous_variant	Exon 1 of 2	ENST00000366609.4	NP_892017.2
IRF2BP2	NM_001077397.1	c.828G>A	p.Ala276Ala	synonymous_variant	Exon 1 of 2		NP_001070865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BP2	ENST00000366609.4	c.828G>A	p.Ala276Ala	synonymous_variant	Exon 1 of 2	1	NM_182972.3	ENSP00000355568.3
IRF2BP2	ENST00000366610.8	c.828G>A	p.Ala276Ala	synonymous_variant	Exon 1 of 2	1		ENSP00000355569.3
ENSG00000228830	ENST00000436039.1	n.631-754C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 131388 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1370208 Hom.: 0 Cov.: 37 AF XY: 0.00000148 AC XY: 1 AN XY: 677414

African (AFR) AF: 0.00 AC: 0 AN: 27934

American (AMR) AF: 0.00 AC: 0 AN: 32842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23530

East Asian (EAS) AF: 0.00 AC: 0 AN: 32986

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4552

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076894

Other (OTH) AF: 0.00 AC: 0 AN: 56820

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4636; hg19: chr1-234744413;