rs10485609

Variant names:

• chr20-49049075-A-G
• rs10485609
• NM_001316.4:c.-12+2652A>G

Variant summary

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

The NM_001316.4(CSE1L):​c.-12+2652A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,118 control chromosomes in the GnomAD database, including 3,720 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 0.22 (3720 hom., cov: 32)
• Consequence: CSE1L NM_001316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 10 publications found

Genes affected

CSE1L (HGNC:2431): (chromosome segregation 1 like) Proteins that carry a nuclear localization signal (NLS) are transported into the nucleus by the importin-alpha/beta heterodimer. Importin-alpha binds the NLS, while importin-beta mediates translocation through the nuclear pore complex. After translocation, RanGTP binds importin-beta and displaces importin-alpha. Importin-alpha must then be returned to the cytoplasm, leaving the NLS protein behind. The protein encoded by this gene binds strongly to NLS-free importin-alpha, and this binding is released in the cytoplasm by the combined action of RANBP1 and RANGAP1. In addition, the encoded protein may play a role both in apoptosis and in cell proliferation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316.4. 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
	CSE1L	NM_001316.4	MANE Select	c.-12+2652A>G		intron	N/A	NP_001307.2
	CSE1L	NM_001362762.2		c.-12+2652A>G		intron	N/A	NP_001349691.1
	CSE1L	NM_001256135.2		c.-12+2652A>G		intron	N/A	NP_001243064.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSE1L	ENST00000262982.3	TSL:1 MANE Select	c.-12+2652A>G		intron	N/A	ENSP00000262982.2
	CSE1L	ENST00000396192.7	TSL:5	c.-12+2652A>G		intron	N/A	ENSP00000379495.3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32999 AN: 152000 Hom.: 3718 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0508

Gnomad SAS AF: 0.0889

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.217 AC: 33018 AN: 152118 Hom.: 3720 Cov.: 32 AF XY: 0.212 AC XY: 15744 AN XY: 74368

African (AFR) AF: 0.230 AC: 9543 AN: 41500

American (AMR) AF: 0.171 AC: 2607 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3470

East Asian (EAS) AF: 0.0507 AC: 263 AN: 5184

South Asian (SAS) AF: 0.0898 AC: 433 AN: 4822

European-Finnish (FIN) AF: 0.226 AC: 2388 AN: 10564

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16381 AN: 67974

Other (OTH) AF: 0.176 AC: 371 AN: 2112

Alfa AF: 0.234 Hom.: 1083

Bravo AF: 0.213

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		2.3
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: rs10485609; hg19: chr20-47665612;