Genetic Variant IRF2BPL:p.Arg188Gly (chr14-77027231-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024496.4(IRF2BPL):c.562C>G(p.Arg188Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,449,508 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

IRF2BPL
NM_024496.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.947

Publications

0 publications found

Variant links:

Genes affected

IRF2BPL (HGNC:14282): (interferon regulatory factor 2 binding protein like) This gene encodes a transcription factor that may play a role in regulating female reproductive function. [provided by RefSeq, Jun 2012]

IRF2BPL links:

LINC02289 (HGNC:53205): (long intergenic non-protein coding RNA 2289)

LINC02289 links:

LOC107984638 (HGNC:):

LOC107984638 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
IRF2BPL	NM_024496.4 link	c.562C>G	p.Arg188Gly	missense_variant	Exon 1 of 1	ENST00000238647.5	NP_078772.1
LOC107984638	NR_190000.1 link	n.-237G>C		upstream_gene_variant
LOC107984638	NR_190001.1 link	n.-237G>C		upstream_gene_variant
LOC107984638	NR_190002.1 link	n.-237G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BPL	ENST00000238647.5 link	c.562C>G	p.Arg188Gly	missense_variant	Exon 1 of 1	6	NM_024496.4	ENSP00000238647.3
LINC02289	ENST00000716908.1 link	n.304+13823C>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1449508

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

720856

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32418

American (AMR)

AF:

0.00

AC:

AN:

43126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25508

East Asian (EAS)

AF:

0.00

AC:

AN:

38662

South Asian (SAS)

AF:

0.00

AC:

AN:

85310

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5516

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1106824

Other (OTH)

AF:

0.00

AC:

AN:

59724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

0.0061

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.13

Eigen

Benign

0.12

Eigen_PC

Benign

0.055

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.74

M_CAP

Pathogenic

0.94

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.75

PhyloP100

0.95

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.29

Sift

Benign

0.032

Sift4G

Uncertain

0.011

Vest4

0.31

ClinPred

0.41

GERP RS

2.7

Varity_R

0.43

gMVP

0.72

Mutation Taster

=63/37

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over