20-49049075-A-G

Position:

• chr20-49049075-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSE1L	NM_001316.4	c.-12+2652A>G		intron_variant		ENST00000262982.3	NP_001307.2
CSE1L	NM_001256135.2	c.-12+2652A>G		intron_variant			NP_001243064.1
CSE1L	NM_001362762.2	c.-12+2652A>G		intron_variant			NP_001349691.1
CSE1L	NR_045796.2	n.112+2652A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSE1L	ENST00000262982.3	c.-12+2652A>G		intron_variant		1	NM_001316.4	ENSP00000262982	P1
CSE1L	ENST00000396192.7	c.-12+2652A>G		intron_variant		5		ENSP00000379495

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

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.0507

Gnomad4 SAS AF: 0.0898

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.176

Alfa AF: 0.233 Hom.: 1012

Bravo AF: 0.213

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.82

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: rs10485609; hg19: chr20-47665612;