rs950114

Variant names:

• chr1-201871082-T-C
• rs950114
• NM_018085.5:c.2410-79T>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.2410-79T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,426,930 control chromosomes in the GnomAD database, including 3,027 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 0.035 (301 hom., cov: 31)
  • Exomes 𝑓: 0.037 (2726 hom.)
• Consequence: IPO9 NM_018085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO9	NM_018085.5	c.2410-79T>C		intron_variant	Intron 18 of 23	ENST00000361565.9	NP_060555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO9	ENST00000361565.9	c.2410-79T>C		intron_variant	Intron 18 of 23	1	NM_018085.5	ENSP00000354742.4

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5265 AN: 152150 Hom.: 300 Cov.: 31

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.0932

Gnomad FIN AF: 0.00932

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.0368

GnomAD4 exome AF: 0.0368 AC: 46933 AN: 1274662 Hom.: 2726 Cov.: 18 AF XY: 0.0383 AC XY: 24355 AN XY: 635664

African (AFR) AF: 0.0228 AC: 667 AN: 29230

American (AMR) AF: 0.0556 AC: 2158 AN: 38806

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 1670 AN: 21814

East Asian (EAS) AF: 0.310 AC: 11941 AN: 38542

South Asian (SAS) AF: 0.0875 AC: 6525 AN: 74560

European-Finnish (FIN) AF: 0.0127 AC: 609 AN: 47856

Middle Eastern (MID) AF: 0.0477 AC: 252 AN: 5282

European-Non Finnish (NFE) AF: 0.0214 AC: 20680 AN: 964940

Other (OTH) AF: 0.0453 AC: 2431 AN: 53632

GnomAD4 genome AF: 0.0347 AC: 5280 AN: 152268 Hom.: 301 Cov.: 31 AF XY: 0.0372 AC XY: 2767 AN XY: 74454

African (AFR) AF: 0.0214 AC: 889 AN: 41554

American (AMR) AF: 0.0333 AC: 509 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1446 AN: 5162

South Asian (SAS) AF: 0.0937 AC: 452 AN: 4826

European-Finnish (FIN) AF: 0.00932 AC: 99 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0223 AC: 1517 AN: 68028

Other (OTH) AF: 0.0392 AC: 83 AN: 2116

Alfa AF: 0.0334 Hom.: 855

Bravo AF: 0.0373

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.10
DANN	Benign	0.35
PhyloP100		-0.77
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: rs950114; hg19: chr1-201840210; COSMIC: COSV64233174; COSMIC: COSV64233174;