14-24188020-C-T

Position:

• chr14-24188020-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024658.4(IPO4):​c.278+196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 767,480 control chromosomes in the GnomAD database, including 38,835 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (7277 hom., cov: 32)
  • Exomes 𝑓: 0.31 (31558 hom.)
• Consequence: IPO4 NM_024658.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554

Genes affected

IPO4 (HGNC:19426): (importin 4) Predicted to enable nuclear import signal receptor activity and nuclear localization sequence binding activity. Involved in DNA replication-dependent chromatin assembly; DNA replication-independent chromatin assembly; and protein import into nucleus. Located in chromatin. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO4	NM_024658.4	c.278+196G>A		intron_variant		ENST00000354464.11	NP_078934.3
IPO4	NR_051979.2	n.307+196G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO4	ENST00000354464.11	c.278+196G>A		intron_variant		1	NM_024658.4	ENSP00000346453	P1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46675 AN: 151918 Hom.: 7268 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.313 AC: 192628 AN: 615444 Hom.: 31558 Cov.: 8 AF XY: 0.317 AC XY: 101316 AN XY: 319526

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.295

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.307 AC: 46723 AN: 152036 Hom.: 7277 Cov.: 32 AF XY: 0.305 AC XY: 22632 AN XY: 74316

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.286

Alfa AF: 0.300 Hom.: 14277

Bravo AF: 0.313

Asia WGS AF: 0.461 AC: 1601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.80

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: rs2295977; hg19: chr14-24657226;