rs8722

Variant names:

• chr1-234608504-G-A
• rs8722
• NM_182972.3:c.991C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-234608504-G-A
• chr1-234608504-G-C

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.991C>T​(p.Leu331Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,608,560 control chromosomes in the GnomAD database, including 38,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2668 hom., cov: 33)
  • Exomes 𝑓: 0.22 (36171 hom.)
• Consequence: IRF2BP2 NM_182972.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.511
• Publications: 14 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=-0.57).
• BP6: Variant 1-234608504-G-A is Benign according to our data. Variant chr1-234608504-G-A is described in ClinVar as Benign. ClinVar VariationId is 402982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.511 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 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.991C>T	p.Leu331Leu	synonymous	Exon 1 of 2	NP_892017.2	Q7Z5L9-1
	IRF2BP2	NM_001077397.1		c.991C>T	p.Leu331Leu	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.991C>T	p.Leu331Leu	synonymous	Exon 1 of 2	ENSP00000355568.3	Q7Z5L9-1
	IRF2BP2	ENST00000366610.8	TSL:1	c.991C>T	p.Leu331Leu	synonymous	Exon 1 of 2	ENSP00000355569.3	Q7Z5L9-2
	IRF2BP2	ENST00000947260.1		c.991C>T	p.Leu331Leu	synonymous	Exon 1 of 2	ENSP00000617319.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25369 AN: 152106 Hom.: 2671 Cov.: 33

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.189 AC: 45928 AN: 242520 AF XY: 0.192

Gnomad AFR exome AF: 0.0345

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.231

Gnomad EAS exome AF: 0.204

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.216 AC: 315187 AN: 1456336 Hom.: 36171 Cov.: 32 AF XY: 0.213 AC XY: 154599 AN XY: 724136

African (AFR) AF: 0.0353 AC: 1176 AN: 33298

American (AMR) AF: 0.130 AC: 5725 AN: 44206

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 5952 AN: 25996

East Asian (EAS) AF: 0.227 AC: 8958 AN: 39426

South Asian (SAS) AF: 0.101 AC: 8618 AN: 85494

European-Finnish (FIN) AF: 0.255 AC: 13338 AN: 52296

Middle Eastern (MID) AF: 0.158 AC: 911 AN: 5758

European-Non Finnish (NFE) AF: 0.233 AC: 258057 AN: 1109676

Other (OTH) AF: 0.207 AC: 12452 AN: 60186

GnomAD4 genome AF: 0.167 AC: 25361 AN: 152224 Hom.: 2668 Cov.: 33 AF XY: 0.167 AC XY: 12408 AN XY: 74406

African (AFR) AF: 0.0423 AC: 1757 AN: 41580

American (AMR) AF: 0.168 AC: 2574 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3472

East Asian (EAS) AF: 0.210 AC: 1086 AN: 5168

South Asian (SAS) AF: 0.100 AC: 482 AN: 4818

European-Finnish (FIN) AF: 0.255 AC: 2698 AN: 10592

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15317 AN: 67988

Other (OTH) AF: 0.189 AC: 399 AN: 2110

Alfa AF: 0.204 Hom.: 6969

Bravo AF: 0.158

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs8722; hg19: chr1-234744250; COSMIC: COSV64014695; COSMIC: COSV64014695;