Genetic Variant CSDE1:c.2350-5C>T (chr1-114718221-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001007553.3(CSDE1):c.2350-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000757 in 1,611,226 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. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

CSDE1
NM_001007553.3 splice_region, intron

Scores

Splicing: ADA: 0.0001064

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.662

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

CSDE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-114718221-G-A is Benign according to our data. Variant chr1-114718221-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3054211.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000501 (76/151774) while in subpopulation AFR AF = 0.00181 (75/41386). AF 95% confidence interval is 0.00148. There are 0 homozygotes in GnomAd4. There are 39 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 76 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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.000501

AC:

AN:

151658

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000105

AC:

AN:

248058

AF XY:

0.0000298

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1459452

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

725994

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

33304

American (AMR)

AF:

0.0000676

AC:

AN:

44380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111002

Other (OTH)

AF:

0.0000663

AC:

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000501

AC:

AN:

151774

Hom.:

Cov.:

AF XY:

0.000526

AC XY:

AN XY:

74130

show subpopulations

African (AFR)

AF:

0.00181

AC:

AN:

41386

American (AMR)

AF:

0.0000655

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67918

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000203

Hom.:

Bravo

AF:

0.000461

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CSDE1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.3

(source)

DANN

Benign

0.83

PhyloP100

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.022

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over