Genetic Variant NM_024496.4:c.514G>C (chr14-77027279-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024496.4(IRF2BPL):c.514G>C(p.Glu172Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,426,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IRF2BPL
NM_024496.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.69

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31862974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BPL	NM_024496.4 link	c.514G>C	p.Glu172Gln	missense_variant	Exon 1 of 1	ENST00000238647.5	NP_078772.1	Q9H1B7
LOC107984638	NR_190000.1 link	n.-189C>G		upstream_gene_variant
LOC107984638	NR_190001.1 link	n.-189C>G		upstream_gene_variant
LOC107984638	NR_190002.1 link	n.-189C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BPL	ENST00000238647.5 link	c.514G>C	p.Glu172Gln	missense_variant	Exon 1 of 1	6	NM_024496.4	ENSP00000238647.3		Q9H1B7
LINC02289	ENST00000716908.1 link	n.304+13775G>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1426254

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30860

American (AMR)

AF:

0.00

AC:

AN:

38292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24148

East Asian (EAS)

AF:

0.00

AC:

AN:

37680

South Asian (SAS)

AF:

0.00

AC:

AN:

82730

European-Finnish (FIN)

AF:

0.0000202

AC:

AN:

49436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4748

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1099678

Other (OTH)

AF:

0.00

AC:

AN:

58682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.024

Eigen

Benign

0.022

Eigen_PC

Benign

0.086

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.90

PhyloP100

2.7

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.91

REVEL

Benign

0.070

Sift

Uncertain

0.028

Sift4G

Benign

0.33

Polyphen

0.83

Vest4

0.33

MutPred

0.24

Loss of methylation at R170 (P = 0.0797);

MVP

0.12

MPC

1.0

ClinPred

0.64

GERP RS

3.7

Varity_R

0.18

gMVP

0.63

Mutation Taster

=83/17

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