1-43961276-G-A

Variant names:

• chr1-43961276-G-A
• rs2906596
• NM_014652.4:c.2344+14G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014652.4(IPO13):​c.2344+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 1,603,624 control chromosomes in the GnomAD database, including 665,196 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 0.86 (56468 hom., cov: 32)
  • Exomes 𝑓: 0.91 (608728 hom.)
• Consequence: IPO13 NM_014652.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 15 publications found

Genes affected

IPO13 (HGNC:16853): (importin 13) This gene encodes a member of the importin-beta family of nuclear transport proteins. The encoded protein mediates the import of specific cargo proteins from the cytoplasm to the nucleus and is dependent on the Ras-related nuclear protein-GTPase system. The encoded protein is also involved in nuclear export of the eukaryotic translation initiation factor 1A.[provided by RefSeq, Mar 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014652.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO13	NM_014652.4	MANE Select	c.2344+14G>A		intron	N/A	NP_055467.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO13	ENST00000372343.8	TSL:1 MANE Select	c.2344+14G>A		intron	N/A	ENSP00000361418.3

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130163 AN: 152048 Hom.: 56447 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.866

GnomAD2 exomes AF: 0.889 AC: 223284 AN: 251222 AF XY: 0.895

Gnomad AFR exome AF: 0.706

Gnomad AMR exome AF: 0.848

Gnomad ASJ exome AF: 0.929

Gnomad EAS exome AF: 0.848

Gnomad FIN exome AF: 0.883

Gnomad NFE exome AF: 0.928

Gnomad OTH exome AF: 0.893

GnomAD4 exome AF: 0.915 AC: 1327551 AN: 1451458 Hom.: 608728 Cov.: 32 AF XY: 0.915 AC XY: 661721 AN XY: 722874

African (AFR) AF: 0.698 AC: 23171 AN: 33206

American (AMR) AF: 0.850 AC: 38000 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 24195 AN: 26064

East Asian (EAS) AF: 0.800 AC: 31686 AN: 39632

South Asian (SAS) AF: 0.899 AC: 77358 AN: 86054

European-Finnish (FIN) AF: 0.885 AC: 47194 AN: 53300

Middle Eastern (MID) AF: 0.867 AC: 4976 AN: 5742

European-Non Finnish (NFE) AF: 0.931 AC: 1026957 AN: 1102714

Other (OTH) AF: 0.900 AC: 54014 AN: 60042

GnomAD4 genome AF: 0.856 AC: 130239 AN: 152166 Hom.: 56468 Cov.: 32 AF XY: 0.855 AC XY: 63582 AN XY: 74404

African (AFR) AF: 0.708 AC: 29362 AN: 41464

American (AMR) AF: 0.872 AC: 13339 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3222 AN: 3472

East Asian (EAS) AF: 0.834 AC: 4320 AN: 5182

South Asian (SAS) AF: 0.903 AC: 4351 AN: 4816

European-Finnish (FIN) AF: 0.875 AC: 9279 AN: 10608

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.932 AC: 63395 AN: 68018

Other (OTH) AF: 0.867 AC: 1832 AN: 2112

Alfa AF: 0.894 Hom.: 22527

Bravo AF: 0.849

Asia WGS AF: 0.860 AC: 2991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.1
DANN	Benign	0.76
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2906596; hg19: chr1-44426948;