Genetic Variant IRF2BPL:p.Gln127Lys (chr14-77027414-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024496.4(IRF2BPL):c.379C>A(p.Gln127Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IRF2BPL
NM_024496.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.62

Publications

1 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17193863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BPL	NM_024496.4 link	c.379C>A	p.Gln127Lys	missense_variant	Exon 1 of 1	ENST00000238647.5	NP_078772.1	Q9H1B7
LOC107984638	NR_190000.1 link	n.-54G>T		upstream_gene_variant
LOC107984638	NR_190001.1 link	n.-54G>T		upstream_gene_variant
LOC107984638	NR_190002.1 link	n.-54G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BPL	ENST00000238647.5 link	c.379C>A	p.Gln127Lys	missense_variant	Exon 1 of 1	6	NM_024496.4	ENSP00000238647.3		Q9H1B7
LINC02289	ENST00000716908.1 link	n.304+13640C>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

68956

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1331536

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

656920

African (AFR)

AF:

0.00

AC:

AN:

26738

American (AMR)

AF:

0.00

AC:

AN:

28024

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23136

East Asian (EAS)

AF:

0.00

AC:

AN:

29270

South Asian (SAS)

AF:

0.00

AC:

AN:

73310

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4120

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047026

Other (OTH)

AF:

0.00

AC:

AN:

54556

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.041

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.47

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

2.6

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.67

REVEL

Benign

0.061

Sift

Uncertain

0.012

Sift4G

Benign

0.65

Polyphen

0.90

Vest4

0.38

MutPred

0.29

Gain of ubiquitination at Q127 (P = 0.0031);

MVP

0.043

MPC

1.2

ClinPred

0.25

GERP RS

2.2

Varity_R

0.27

gMVP

0.80

Mutation Taster

=82/18

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over