1-114718221-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001007553.3(CSDE1):​c.2350-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,611,220 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (7 hom.)
• Consequence: CSDE1 NM_001007553.3 splice_region, intron
• Scores: Splicing: ADA: 0.001334
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-114718221-G-T is Benign according to our data. Variant chr1-114718221-G-T is described in ClinVar as Benign. ClinVar VariationId is 721068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00192 (292/151774) while in subpopulation AMR AF = 0.00623 (95/15258). AF 95% confidence interval is 0.00521. There are 0 homozygotes in GnomAd4. There are 153 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 292 AD gene.

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>A		splice_region intron	N/A	NP_001007554.1	O75534-1
	CSDE1	NM_001242891.2		c.2488-5C>A		splice_region intron	N/A	NP_001229820.1	O75534-4
	CSDE1	NM_001130523.3		c.2395-5C>A		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>A		splice_region intron	N/A	ENSP00000351329.4	O75534-1
	CSDE1	ENST00000369530.5	TSL:1	c.2395-5C>A		splice_region intron	N/A	ENSP00000358543.1	O75534-3
	CSDE1	ENST00000438362.7	TSL:1	c.2350-5C>A		splice_region intron	N/A	ENSP00000407724.3	O75534-1

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 292 AN: 151658 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000945

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00623

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00213

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00174 AC: 431 AN: 248058 AF XY: 0.00166

Gnomad AFR exome AF: 0.000742

Gnomad AMR exome AF: 0.00290

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.00269

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00239 AC: 3495 AN: 1459446 Hom.: 7 Cov.: 31 AF XY: 0.00232 AC XY: 1683 AN XY: 725992

African (AFR) AF: 0.000751 AC: 25 AN: 33304

American (AMR) AF: 0.00302 AC: 134 AN: 44380

Ashkenazi Jewish (ASJ) AF: 0.0000767 AC: 2 AN: 26076

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

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85616

European-Finnish (FIN) AF: 0.0000937 AC: 5 AN: 53346

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5758

European-Non Finnish (NFE) AF: 0.00287 AC: 3187 AN: 1110996

Other (OTH) AF: 0.00226 AC: 136 AN: 60288

GnomAD4 genome AF: 0.00192 AC: 292 AN: 151774 Hom.: 0 Cov.: 32 AF XY: 0.00206 AC XY: 153 AN XY: 74130

African (AFR) AF: 0.000942 AC: 39 AN: 41386

American (AMR) AF: 0.00623 AC: 95 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00213 AC: 145 AN: 67918

Other (OTH) AF: 0.00237 AC: 5 AN: 2108

Alfa AF: 0.00163 Hom.: 0

Bravo AF: 0.00225

EpiCase AF: 0.00251

EpiControl AF: 0.00273

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CSDE1-related disorder (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.2
DANN	Benign	0.80
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.068
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: rs189058114; hg19: chr1-115260842;