chr14-77025590-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_024496.4(IRF2BPL):c.2203A>T(p.Ser735Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,607,468 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S735I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 5 hom. )

Consequence

IRF2BPL
NM_024496.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:4

Conservation

PhyloP100: 0.407

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03294909).

BP6

Variant 14-77025590-T-A is Benign according to our data. Variant chr14-77025590-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1284940.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-77025590-T-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00134 (204/152344) while in subpopulation NFE AF = 0.00219 (149/68032). AF 95% confidence interval is 0.0019. There are 1 homozygotes in GnomAd4. There are 98 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 204 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BPL	NM_024496.4 link	c.2203A>T	p.Ser735Cys	missense_variant	Exon 1 of 1	ENST00000238647.5	NP_078772.1	Q9H1B7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BPL	ENST00000238647.5 link	c.2203A>T	p.Ser735Cys	missense_variant	Exon 1 of 1	6	NM_024496.4	ENSP00000238647.3		Q9H1B7

Frequencies

GnomAD3 genomes

AF:

0.00134

AC:

204

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00109

AC:

267

AN:

244974

AF XY:

0.00102

show subpopulations

Gnomad AFR exome

AF:

0.000434

Gnomad AMR exome

AF:

0.000241

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000327

Gnomad NFE exome

AF:

0.00214

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.00234

AC:

3400

AN:

1455124

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

1662

AN XY:

723708

show subpopulations

Gnomad4 AFR exome

AF:

0.000393

AC:

AN:

33118

Gnomad4 AMR exome

AF:

0.000277

AC:

AN:

43366

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25736

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39624

Gnomad4 SAS exome

AF:

0.0000117

AC:

AN:

85542

Gnomad4 FIN exome

AF:

0.000544

AC:

AN:

53268

Gnomad4 NFE exome

AF:

0.00296

AC:

3283

AN:

1108658

Gnomad4 Remaining exome

AF:

0.00103

AC:

AN:

60090

Heterozygous variant carriers

194

388

581

775

969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<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

AF:

0.00134

AC:

204

AN:

152344

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000794

AC:

0.000793613

AN:

0.000793613

Gnomad4 AMR

AF:

0.00105

AC:

0.00104575

AN:

0.00104575

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.000565

AC:

0.000564865

AN:

0.000564865

Gnomad4 NFE

AF:

0.00219

AC:

0.00219015

AN:

0.00219015

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome 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

Alfa

AF:

0.00178

Hom.:

Bravo

AF:

0.00124

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00122

AC:

148

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:3

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IRF2BPL: BS1 -

IRF2BPL-related disorder

Benign:1

Mar 26, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.062

MetaRNN

Benign

0.033

MetaSVM

Uncertain

-0.15

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.27

Sift

Uncertain

0.020

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.54

MVP

0.21

MPC

0.81

ClinPred

0.051

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.32

gMVP

0.48

Mutation Taster

=79/21

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over