Genetic Variant CSDE1:c.2053-4T>C (chr1-114719746-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 204 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSDE1	NM_001007553.3 link	c.2053-4T>C		splice_region_variant, intron_variant	Intron 17 of 19	ENST00000358528.9	NP_001007554.1	O75534-1A0A024R0E2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSDE1	ENST00000358528.9 link	c.2053-4T>C		splice_region_variant, intron_variant	Intron 17 of 19	1	NM_001007553.3	ENSP00000351329.4		O75534-1

Frequencies

GnomAD3 genomes

AF:

0.00136

AC:

204

AN:

149860

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00201

AC:

323

AN:

160880

Hom.:

AF XY:

0.00202

AC XY:

177

AN XY:

87496

show subpopulations

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 SAS exome

AF:

0.000358

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.:

Cov.:

AF XY:

0.00230

AC XY:

1517

AN XY:

659342

show subpopulations

Gnomad4 AFR exome

AF:

0.000171

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.0000884

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000308

Gnomad4 FIN exome

AF:

0.00153

Gnomad4 NFE exome

AF:

0.00272

Gnomad4 OTH exome

AF:

0.00169

GnomAD4 genome

AF:

0.00136

AC:

204

AN:

149960

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

73274

show subpopulations

Gnomad4 AFR

AF:

0.000342

Gnomad4 AMR

AF:

0.000869

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00108

Gnomad4 NFE

AF:

0.00239

Gnomad4 OTH

AF:

0.00194

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00132

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.52

DANN

Benign

0.68

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over