rs4636

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-234608667-C-A
• chr1-234608667-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182972.3(IRF2BP2):​c.828G>T​(p.Ala276Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,521,876 control chromosomes in the GnomAD database, including 94,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7665 hom., cov: 33)
  • Exomes 𝑓: 0.35 (86978 hom.)
• Consequence: IRF2BP2 NM_182972.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ENSG00000228830 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 1-234608667-C-A is Benign according to our data. Variant chr1-234608667-C-A is described in ClinVar as Benign. ClinVar VariationId is 402983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.425 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182972.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2BP2	NM_182972.3	MANE Select	c.828G>T	p.Ala276Ala	synonymous	Exon 1 of 2	NP_892017.2	Q7Z5L9-1
	IRF2BP2	NM_001077397.1		c.828G>T	p.Ala276Ala	synonymous	Exon 1 of 2	NP_001070865.1	Q7Z5L9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2BP2	ENST00000366609.4	TSL:1 MANE Select	c.828G>T	p.Ala276Ala	synonymous	Exon 1 of 2	ENSP00000355568.3	Q7Z5L9-1
	IRF2BP2	ENST00000366610.8	TSL:1	c.828G>T	p.Ala276Ala	synonymous	Exon 1 of 2	ENSP00000355569.3	Q7Z5L9-2
	IRF2BP2	ENST00000947260.1		c.828G>T	p.Ala276Ala	synonymous	Exon 1 of 2	ENSP00000617319.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46099 AN: 152042 Hom.: 7666 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.332

GnomAD2 exomes AF: 0.356 AC: 46831 AN: 131388 AF XY: 0.358

Gnomad AFR exome AF: 0.215

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.436

Gnomad EAS exome AF: 0.257

Gnomad FIN exome AF: 0.393

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.387

GnomAD4 exome AF: 0.352 AC: 482618 AN: 1369716 Hom.: 86978 Cov.: 37 AF XY: 0.351 AC XY: 237540 AN XY: 677110

African (AFR) AF: 0.175 AC: 4886 AN: 27930

American (AMR) AF: 0.299 AC: 9793 AN: 32804

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 9860 AN: 23514

East Asian (EAS) AF: 0.243 AC: 8017 AN: 32968

South Asian (SAS) AF: 0.282 AC: 21506 AN: 76374

European-Finnish (FIN) AF: 0.365 AC: 13963 AN: 38230

Middle Eastern (MID) AF: 0.386 AC: 1755 AN: 4546

European-Non Finnish (NFE) AF: 0.365 AC: 393001 AN: 1076562

Other (OTH) AF: 0.349 AC: 19837 AN: 56788

GnomAD4 genome AF: 0.303 AC: 46106 AN: 152160 Hom.: 7665 Cov.: 33 AF XY: 0.305 AC XY: 22683 AN XY: 74380

African (AFR) AF: 0.180 AC: 7470 AN: 41538

American (AMR) AF: 0.334 AC: 5103 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1471 AN: 3468

East Asian (EAS) AF: 0.220 AC: 1139 AN: 5176

South Asian (SAS) AF: 0.267 AC: 1292 AN: 4832

European-Finnish (FIN) AF: 0.373 AC: 3949 AN: 10586

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.362 AC: 24588 AN: 67954

Other (OTH) AF: 0.332 AC: 702 AN: 2114

Alfa AF: 0.334 Hom.: 1574

Bravo AF: 0.297

Asia WGS AF: 0.247 AC: 860 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Immunodeficiency, common variable, 14 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.6
DANN	Benign	0.91
PhyloP100		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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; COSMIC: COSV64014518; COSMIC: COSV64014518;