1-114718221-G-C

Variant names:

• chr1-114718221-G-C
• rs189058114
• NM_001007553.3:c.2350-5C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001007553.3(CSDE1):​c.2350-5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CSDE1 NM_001007553.3 splice_region, intron
• Scores: Splicing: ADA: 0.001151
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662
• Publications: 0 publications found

Genes affected

CSDE1 (HGNC:29905): (cold shock domain containing E1) Enables RNA stem-loop binding activity. Involved in IRES-dependent viral translational initiation; nuclear-transcribed mRNA catabolic process, no-go decay; and stress granule assembly. Located in Golgi apparatus; cytosol; and plasma membrane. Part of CRD-mediated mRNA stability complex. [provided by Alliance of Genome Resources, Apr 2022]

CSDE1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007553.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSDE1	NM_001007553.3	MANE Select	c.2350-5C>G		splice_region intron	N/A	NP_001007554.1	O75534-1
	CSDE1	NM_001242891.2		c.2488-5C>G		splice_region intron	N/A	NP_001229820.1	O75534-4
	CSDE1	NM_001130523.3		c.2395-5C>G		splice_region intron	N/A	NP_001123995.1	O75534-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSDE1	ENST00000358528.9	TSL:1 MANE Select	c.2350-5C>G		splice_region intron	N/A	ENSP00000351329.4	O75534-1
	CSDE1	ENST00000369530.5	TSL:1	c.2395-5C>G		splice_region intron	N/A	ENSP00000358543.1	O75534-3
	CSDE1	ENST00000438362.7	TSL:1	c.2350-5C>G		splice_region intron	N/A	ENSP00000407724.3	O75534-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459452 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725994

African (AFR) AF: 0.00 AC: 0 AN: 33304

American (AMR) AF: 0.0000225 AC: 1 AN: 44380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111002

Other (OTH) AF: 0.00 AC: 0 AN: 60288

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.7
DANN	Benign	0.72
PhyloP100		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.046
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: rs189058114; hg19: chr1-115260842;