chr14-77026678-G-C

Variant names:

• chr14-77026678-G-C
• rs1555377336
• NM_024496.4:c.1115C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_024496.4(IRF2BPL):​c.1115C>G​(p.Pro372Arg) variant causes a missense change involving the alteration of a 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: 33)
• Consequence: IRF2BPL NM_024496.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.33
• Publications: 2 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811
• PP5: Variant 14-77026678-G-C is Pathogenic according to our data. Variant chr14-77026678-G-C is described in ClinVar as Pathogenic. ClinVar VariationId is 559611.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024496.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2BPL	NM_024496.4	MANE Select	c.1115C>G	p.Pro372Arg	missense	Exon 1 of 1	NP_078772.1	Q9H1B7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2BPL	ENST00000238647.5	TSL:6 MANE Select	c.1115C>G	p.Pro372Arg	missense	Exon 1 of 1	ENSP00000238647.3	Q9H1B7
	LINC02289	ENST00000716908.1		n.304+14376C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.28
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.080	T
Polyphen		1.0	D
Vest4		0.90
MutPred		0.38		Gain of MoRF binding (P = 0.0064)
MVP		0.33
MPC		0.89
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.69
gMVP		0.90
Mutation Taster		=14/86	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: rs1555377336; hg19: chr14-77493021;