1-234609333-C-T

Variant names:

• chr1-234609333-C-T
• rs1479179719
• NM_182972.3:c.162G>A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2 BP4_Strong BP6_Moderate BP7 BS2

The NM_182972.3(IRF2BP2):​c.162G>A​(p.Glu54Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000363 in 1,377,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: IRF2BP2 NM_182972.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.616

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:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 1-234609333-C-T is Benign according to our data. Variant chr1-234609333-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2052216.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.616 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BP2	NM_182972.3	c.162G>A	p.Glu54Glu	synonymous_variant	Exon 1 of 2	ENST00000366609.4	NP_892017.2
IRF2BP2	NM_001077397.1	c.162G>A	p.Glu54Glu	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.162G>A	p.Glu54Glu	synonymous_variant	Exon 1 of 2	1	NM_182972.3	ENSP00000355568.3
IRF2BP2	ENST00000366610.7	c.162G>A	p.Glu54Glu	synonymous_variant	Exon 1 of 2	1		ENSP00000355569.3
ENSG00000228830	ENST00000436039.1	n.631-88C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000363 AC: 5 AN: 1377342 Hom.: 0 Cov.: 34 AF XY: 0.00000293 AC XY: 2 AN XY: 682158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000466

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 17, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs1479179719; hg19: chr1-234745079;