14-77027279-C-G

Variant names:

• chr14-77027279-C-G
• rs1448259271
• NM_024496.4:c.514G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 0 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: 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	c.514G>C	p.Glu172Gln	missense_variant	Exon 1 of 1	ENST00000238647.5	NP_078772.1
LOC107984638	NR_190000.1	n.-189C>G		upstream_gene_variant
LOC107984638	NR_190001.1	n.-189C>G		upstream_gene_variant
LOC107984638	NR_190002.1	n.-189C>G		upstream_gene_variant

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1426254 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 709122

African (AFR) AF: 0.00 AC: 0 AN: 30860

American (AMR) AF: 0.00 AC: 0 AN: 38292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24148

East Asian (EAS) AF: 0.00 AC: 0 AN: 37680

South Asian (SAS) AF: 0.00 AC: 0 AN: 82730

European-Finnish (FIN) AF: 0.0000202 AC: 1 AN: 49436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4748

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1099678

Other (OTH) AF: 0.00 AC: 0 AN: 58682

GnomAD4 genome Cov.: 33

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	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.022
Eigen_PC	Benign	0.086
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.7
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.070
Sift	Uncertain	0.028	D
Sift4G	Benign	0.33	T
Polyphen		0.83	P
Vest4		0.33
MutPred		0.24		Loss of methylation at R170 (P = 0.0797);
MVP		0.12
MPC		1.0
ClinPred		0.64	D
GERP RS		3.7
Varity_R		0.18
gMVP		0.63
Mutation Taster		=83/17	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

Other links and lift over

dbSNP: rs1448259271; hg19: chr14-77493622;