1-234609327-C-T

Variant names:

• chr1-234609327-C-T
• rs773014796
• NM_182972.3:c.168G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_182972.3(IRF2BP2):​c.168G>A​(p.Ala56Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,371,012 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: 0.0000022 (0 hom.)
• Consequence: IRF2BP2 NM_182972.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.437
• Publications: 0 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]

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

ENSG00000228830 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-234609327-C-T is Benign according to our data. Variant chr1-234609327-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2965638.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.437 with no splicing effect.

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.168G>A	p.Ala56Ala	synonymous	Exon 1 of 2	NP_892017.2	Q7Z5L9-1
	IRF2BP2	NM_001077397.1		c.168G>A	p.Ala56Ala	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.168G>A	p.Ala56Ala	synonymous	Exon 1 of 2	ENSP00000355568.3	Q7Z5L9-1
	IRF2BP2	ENST00000366610.8	TSL:1	c.168G>A	p.Ala56Ala	synonymous	Exon 1 of 2	ENSP00000355569.3	Q7Z5L9-2
	IRF2BP2	ENST00000947260.1		c.168G>A	p.Ala56Ala	synonymous	Exon 1 of 2	ENSP00000617319.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000149 AC: 2 AN: 133780 AF XY: 0.0000266

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000454

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1371012 Hom.: 0 Cov.: 34 AF XY: 0.00000295 AC XY: 2 AN XY: 678494

African (AFR) AF: 0.00 AC: 0 AN: 27876

American (AMR) AF: 0.0000301 AC: 1 AN: 33250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23904

East Asian (EAS) AF: 0.00 AC: 0 AN: 30728

South Asian (SAS) AF: 0.00 AC: 0 AN: 76902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48074

Middle Eastern (MID) AF: 0.000225 AC: 1 AN: 4444

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069412

Other (OTH) AF: 0.0000177 AC: 1 AN: 56422

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.6
DANN	Benign	0.88
PhyloP100		-0.44
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs773014796; hg19: chr1-234745073;