1-234609263-A-G

Variant names:

• chr1-234609263-A-G
• rs7545855
• NM_182972.3:c.232T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182972.3(IRF2BP2):​c.232T>C​(p.Ser78Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,377,458 control chromosomes in the GnomAD database, including 352,861 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41039 hom., cov: 32)
  • Exomes 𝑓: 0.71 (311822 hom.)
• Consequence: IRF2BP2 NM_182972.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.495
• Publications: 20 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]

ENSG00000228830 (HGNC:):

LINC00184 (HGNC:37192): (long intergenic non-protein coding RNA 184)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3392341E-6).
• BP6: Variant 1-234609263-A-G is Benign according to our data. Variant chr1-234609263-A-G is described in ClinVar as Benign. ClinVar VariationId is 402984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2BP2	NM_182972.3	MANE Select	c.232T>C	p.Ser78Pro	missense	Exon 1 of 2	NP_892017.2
	IRF2BP2	NM_001077397.1		c.232T>C	p.Ser78Pro	missense	Exon 1 of 2	NP_001070865.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2BP2	ENST00000366609.4	TSL:1 MANE Select	c.232T>C	p.Ser78Pro	missense	Exon 1 of 2	ENSP00000355568.3
	IRF2BP2	ENST00000366610.8	TSL:1	c.232T>C	p.Ser78Pro	missense	Exon 1 of 2	ENSP00000355569.3
	ENSG00000228830	ENST00000436039.1	TSL:3	n.631-158A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.728 AC: 109668 AN: 150662 Hom.: 41000 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.734

GnomAD2 exomes AF: 0.610 AC: 11605 AN: 19032 AF XY: 0.611

Gnomad AFR exome AF: 0.760

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.701

Gnomad EAS exome AF: 0.178

Gnomad FIN exome AF: 0.725

Gnomad NFE exome AF: 0.696

Gnomad OTH exome AF: 0.666

GnomAD4 exome AF: 0.707 AC: 867342 AN: 1226686 Hom.: 311822 Cov.: 64 AF XY: 0.702 AC XY: 420732 AN XY: 599294

African (AFR) AF: 0.840 AC: 20255 AN: 24126

American (AMR) AF: 0.517 AC: 6135 AN: 11870

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 12756 AN: 17100

East Asian (EAS) AF: 0.278 AC: 7607 AN: 27382

South Asian (SAS) AF: 0.499 AC: 27234 AN: 54596

European-Finnish (FIN) AF: 0.718 AC: 27126 AN: 37798

Middle Eastern (MID) AF: 0.731 AC: 2533 AN: 3466

European-Non Finnish (NFE) AF: 0.729 AC: 729211 AN: 1000446

Other (OTH) AF: 0.691 AC: 34485 AN: 49902

GnomAD4 genome AF: 0.728 AC: 109756 AN: 150772 Hom.: 41039 Cov.: 32 AF XY: 0.718 AC XY: 52866 AN XY: 73584

African (AFR) AF: 0.842 AC: 34825 AN: 41372

American (AMR) AF: 0.621 AC: 9443 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2580 AN: 3446

East Asian (EAS) AF: 0.272 AC: 1357 AN: 4992

South Asian (SAS) AF: 0.488 AC: 2339 AN: 4794

European-Finnish (FIN) AF: 0.715 AC: 7402 AN: 10356

Middle Eastern (MID) AF: 0.736 AC: 212 AN: 288

European-Non Finnish (NFE) AF: 0.735 AC: 49477 AN: 67338

Other (OTH) AF: 0.730 AC: 1525 AN: 2088

Alfa AF: 0.732 Hom.: 4724

Bravo AF: 0.723

ExAC AF: 0.361 AC: 11334

Asia WGS AF: 0.416 AC: 1389 AN: 3326

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.2
DANN	Benign	0.13
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.49
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	1.8	N
REVEL	Benign	0.028
Sift	Benign	1.0	T
Sift4G	Benign	0.95	T
Polyphen		0.0	B
Vest4		0.048
MPC		1.5
ClinPred		0.0033	T
GERP RS		0.22
PromoterAI		-0.11	Neutral
Varity_R		0.099
gMVP		0.15
Mutation Taster		=98/2	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: rs7545855; hg19: chr1-234745009; COSMIC: COSV64014804; COSMIC: COSV64014804;