1-114718221-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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 criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.662

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 292 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSDE1	NM_001007553.3	c.2350-5C>A		splice_region_variant, intron_variant	Intron 19 of 19	ENST00000358528.9	NP_001007554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSDE1	ENST00000358528.9	c.2350-5C>A		splice_region_variant, intron_variant	Intron 19 of 19	1	NM_001007553.3	ENSP00000351329.4

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

GnomAD3 exomes AF: 0.00174 AC: 431 AN: 248058 Hom.: 1 AF XY: 0.00166 AC XY: 223 AN XY: 134122

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 SAS 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

Gnomad4 AFR exome AF: 0.000751

Gnomad4 AMR exome AF: 0.00302

Gnomad4 ASJ exome AF: 0.0000767

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000350

Gnomad4 FIN exome AF: 0.0000937

Gnomad4 NFE exome AF: 0.00287

Gnomad4 OTH exome AF: 0.00226

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

Gnomad4 AFR AF: 0.000942

Gnomad4 AMR AF: 0.00623

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00213

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00163 Hom.: 0

Bravo AF: 0.00225

EpiCase AF: 0.00251

EpiControl AF: 0.00273

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Dec 09, 2021

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Nov 03, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CSDE1-related disorder Benign:1

Aug 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.2
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs189058114; hg19: chr1-115260842;