rs1555377483

Variant names:

• chr14-77027417-G-A
• rs1555377483
• NM_024496.4:c.376C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-77027417-G-A
• chr14-77027417-G-C

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_024496.4(IRF2BPL):​c.376C>T​(p.Gln126*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRF2BPL NM_024496.4 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:3
• Conservation: PhyloP100: 3.15
• Publications: 1 publications found

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]

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

LOC107984638 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 64 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-77027417-G-A is Pathogenic according to our data. Variant chr14-77027417-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 559610.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BPL	NM_024496.4	c.376C>T	p.Gln126*	stop_gained	Exon 1 of 1	ENST00000238647.5	NP_078772.1
LOC107984638	NR_190000.1	n.-51G>A		upstream_gene_variant
LOC107984638	NR_190001.1	n.-51G>A		upstream_gene_variant
LOC107984638	NR_190002.1	n.-51G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BPL	ENST00000238647.5	c.376C>T	p.Gln126*	stop_gained	Exon 1 of 1	6	NM_024496.4	ENSP00000238647.3
LINC02289	ENST00000716908.1	n.304+13637C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1323954 Hom.: 0 Cov.: 65 AF XY: 0.00 AC XY: 0 AN XY: 653072

African (AFR) AF: 0.00 AC: 0 AN: 26552

American (AMR) AF: 0.00 AC: 0 AN: 27452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22962

East Asian (EAS) AF: 0.00 AC: 0 AN: 28856

South Asian (SAS) AF: 0.00 AC: 0 AN: 72604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4030

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1042558

Other (OTH) AF: 0.00 AC: 0 AN: 54264

GnomAD4 genome Cov.: 29

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: no assertion criteria provided

Submissions by phenotype

not provided Pathogenic:2

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures Pathogenic:1

Dec 20, 2018

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.0049
FATHMM_MKL	Benign	0.57	D
PhyloP100		3.1
Vest4		0.078
GERP RS		2.2
Mutation Taster		=0/200	disease causing (ClinVar)

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: rs1555377483; hg19: chr14-77493760;