NM_001007553.3:c.2053-4T>C

Variant names:

• chr1-114719746-A-G
• rs202150406
• NM_001007553.3:c.2053-4T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001007553.3(CSDE1):​c.2053-4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,476,910 control chromosomes in the GnomAD database, including 3 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 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (3 hom.)
• Consequence: CSDE1 NM_001007553.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001060
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0620
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-114719746-A-G is Benign according to our data. Variant chr1-114719746-A-G is described in ClinVar as Benign. ClinVar VariationId is 725517.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00136 (204/149960) while in subpopulation NFE AF = 0.00239 (161/67306). AF 95% confidence interval is 0.00209. There are 0 homozygotes in GnomAd4. There are 89 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 204 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.2053-4T>C		splice_region intron	N/A	NP_001007554.1	O75534-1
	CSDE1	NM_001242891.2		c.2191-4T>C		splice_region intron	N/A	NP_001229820.1	O75534-4
	CSDE1	NM_001130523.3		c.2098-4T>C		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.2053-4T>C		splice_region intron	N/A	ENSP00000351329.4	O75534-1
	CSDE1	ENST00000369530.5	TSL:1	c.2098-4T>C		splice_region intron	N/A	ENSP00000358543.1	O75534-3
	CSDE1	ENST00000438362.7	TSL:1	c.2053-4T>C		splice_region intron	N/A	ENSP00000407724.3	O75534-1

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 204 AN: 149860 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000870

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00239

Gnomad OTH AF: 0.00196

GnomAD2 exomes AF: 0.00201 AC: 323 AN: 160880 AF XY: 0.00202

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00161

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00145

Gnomad NFE exome AF: 0.00316

Gnomad OTH exome AF: 0.00333

GnomAD4 exome AF: 0.00227 AC: 3015 AN: 1326950 Hom.: 3 Cov.: 32 AF XY: 0.00230 AC XY: 1517 AN XY: 659342

African (AFR) AF: 0.000171 AC: 5 AN: 29264

American (AMR) AF: 0.00119 AC: 42 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.0000884 AC: 2 AN: 22612

East Asian (EAS) AF: 0.00 AC: 0 AN: 35958

South Asian (SAS) AF: 0.000308 AC: 23 AN: 74690

European-Finnish (FIN) AF: 0.00153 AC: 70 AN: 45846

Middle Eastern (MID) AF: 0.000192 AC: 1 AN: 5208

European-Non Finnish (NFE) AF: 0.00272 AC: 2780 AN: 1023746

Other (OTH) AF: 0.00169 AC: 92 AN: 54424

GnomAD4 genome AF: 0.00136 AC: 204 AN: 149960 Hom.: 0 Cov.: 32 AF XY: 0.00121 AC XY: 89 AN XY: 73274

African (AFR) AF: 0.000342 AC: 14 AN: 40888

American (AMR) AF: 0.000869 AC: 13 AN: 14968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4746

European-Finnish (FIN) AF: 0.00108 AC: 11 AN: 10228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00239 AC: 161 AN: 67306

Other (OTH) AF: 0.00194 AC: 4 AN: 2064

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.00132

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.52
DANN	Benign	0.68
PhyloP100		0.062
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.26
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: rs202150406; hg19: chr1-115262367;