rs1400875

Variant names:

• chr1-201852315-T-C
• rs1400875
• NM_018085.5:c.603+123T>C

Variant summary

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

The NM_018085.5(IPO9):​c.603+123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 595,946 control chromosomes in the GnomAD database, including 26,832 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 0.28 (6255 hom., cov: 32)
  • Exomes 𝑓: 0.29 (20577 hom.)
• Consequence: IPO9 NM_018085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565
• Publications: 10 publications found

Genes affected

IPO9 (HGNC:19425): (importin 9) Enables nuclear import signal receptor activity. Involved in protein import into nucleus. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO9	NM_018085.5	c.603+123T>C		intron_variant	Intron 5 of 23	ENST00000361565.9	NP_060555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO9	ENST00000361565.9	c.603+123T>C		intron_variant	Intron 5 of 23	1	NM_018085.5	ENSP00000354742.4
IPO9	ENST00000464348.5	n.775+123T>C		intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42712 AN: 151950 Hom.: 6251 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.293 AC: 129926 AN: 443876 Hom.: 20577 AF XY: 0.293 AC XY: 68643 AN XY: 234352

African (AFR) AF: 0.230 AC: 2886 AN: 12564

American (AMR) AF: 0.258 AC: 4365 AN: 16900

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 2585 AN: 13442

East Asian (EAS) AF: 0.102 AC: 3121 AN: 30622

South Asian (SAS) AF: 0.286 AC: 12029 AN: 42024

European-Finnish (FIN) AF: 0.299 AC: 9671 AN: 32336

Middle Eastern (MID) AF: 0.208 AC: 731 AN: 3518

European-Non Finnish (NFE) AF: 0.327 AC: 87458 AN: 267308

Other (OTH) AF: 0.281 AC: 7080 AN: 25162

GnomAD4 genome AF: 0.281 AC: 42730 AN: 152070 Hom.: 6255 Cov.: 32 AF XY: 0.279 AC XY: 20719 AN XY: 74302

African (AFR) AF: 0.230 AC: 9547 AN: 41472

American (AMR) AF: 0.268 AC: 4093 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3466

East Asian (EAS) AF: 0.103 AC: 533 AN: 5164

South Asian (SAS) AF: 0.268 AC: 1290 AN: 4822

European-Finnish (FIN) AF: 0.314 AC: 3310 AN: 10552

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22377 AN: 67992

Other (OTH) AF: 0.249 AC: 525 AN: 2110

Alfa AF: 0.313 Hom.: 4072

Bravo AF: 0.275

Asia WGS AF: 0.163 AC: 564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.2
DANN	Benign	0.66
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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: rs1400875; hg19: chr1-201821443; COSMIC: COSV64233634; COSMIC: COSV64233634;