NM_024496.4:c.2354C>A

Variant names:

• chr14-77025439-G-T
• rs1432066824
• NM_024496.4:c.2354C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024496.4(IRF2BPL):​c.2354C>A​(p.Ala785Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: IRF2BPL NM_024496.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.96

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BPL	NM_024496.4	c.2354C>A	p.Ala785Asp	missense_variant	Exon 1 of 1	ENST00000238647.5	NP_078772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BPL	ENST00000238647.5	c.2354C>A	p.Ala785Asp	missense_variant	Exon 1 of 1	6	NM_024496.4	ENSP00000238647.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000428 AC: 1 AN: 233596 Hom.: 0 AF XY: 0.00000793 AC XY: 1 AN XY: 126114

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000941

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437522 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 713304

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	-0.061	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.40		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.43
MPC		1.2
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.87
gMVP		0.73

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

Other links and lift over

dbSNP: rs1432066824; hg19: chr14-77491782;