chr14-77027417-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024496.4(IRF2BPL):​c.376C>G​(p.Gln126Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000755 in 1,323,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 29)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: IRF2BPL NM_024496.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15

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]

LOC107984638 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23586962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BPL	NM_024496.4	c.376C>G	p.Gln126Glu	missense_variant	Exon 1 of 1	ENST00000238647.5	NP_078772.1
LOC107984638	NR_190000.1	n.-51G>C		upstream_gene_variant
LOC107984638	NR_190001.1	n.-51G>C		upstream_gene_variant
LOC107984638	NR_190002.1	n.-51G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BPL	ENST00000238647.5	c.376C>G	p.Gln126Glu	missense_variant	Exon 1 of 1	6	NM_024496.4	ENSP00000238647.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.55e-7 AC: 1 AN: 1323954 Hom.: 0 Cov.: 65 AF XY: 0.00000153 AC XY: 1 AN XY: 653072

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000347

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.59
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.14
Sift	Uncertain	0.017	D
Sift4G	Benign	1.0	T
Polyphen		0.81	P
Vest4		0.32
MutPred		0.18		Gain of helix (P = 0.0696);
MVP		0.082
MPC		1.0
ClinPred		0.27	T
GERP RS		2.2
Varity_R		0.19
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-77493760;