Genetic Variant CSDE1:c.*1191C>A (chr1-114716978-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001007553.3(CSDE1):c.*1191C>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.111 in 152,726 control chromosomes in the GnomAD database, including 1,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1201 hom., cov: 33)

Exomes 𝑓: 0.18 ( 9 hom. )

Consequence

CSDE1
NM_001007553.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.02

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:

NRAS (HGNC:7989): (NRAS proto-oncogene, GTPase) This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. This shuttling is regulated through palmitoylation and depalmitoylation by the ZDHHC9-GOLGA7 complex. The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. Mutations in this gene have been associated with somatic rectal cancer, follicular thyroid cancer, autoimmune lymphoproliferative syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia. [provided by RefSeq, Jun 2011]

NRAS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 1-114716978-G-T is Benign according to our data. Variant chr1-114716978-G-T is described in ClinVar as [Benign]. Clinvar id is 1228033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSDE1	NM_001007553.3 link	c.*1191C>A		3_prime_UTR_variant	Exon 20 of 20	ENST00000358528.9	NP_001007554.1	O75534-1A0A024R0E2
NRAS	NM_002524.5 link	c.-338C>A		upstream_gene_variant		ENST00000369535.5	NP_002515.1	P01111Q5U091

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSDE1	ENST00000358528 link	c.*1191C>A		3_prime_UTR_variant	Exon 20 of 20	1	NM_001007553.3	ENSP00000351329.4		O75534-1
NRAS	ENST00000369535.5 link	c.-338C>A		upstream_gene_variant		1	NM_002524.5	ENSP00000358548.4		P01111

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16932

AN:

152166

Hom.:

1201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0257

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0896

Gnomad EAS

AF:

0.0896

Gnomad SAS

AF:

0.0754

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.0880

GnomAD4 exome

AF:

0.176

AC:

AN:

442

Hom.:

Cov.:

AF XY:

0.177

AC XY:

AN XY:

260

show subpopulations

Gnomad4 FIN exome

AF:

0.181

Gnomad4 NFE exome

AF:

0.0909

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.111

AC:

16931

AN:

152284

Hom.:

1201

Cov.:

AF XY:

0.111

AC XY:

8257

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0256

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.0896

Gnomad4 EAS

AF:

0.0900

Gnomad4 SAS

AF:

0.0754

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.0875

Alfa

AF:

0.138

Hom.:

1945

Bravo

AF:

0.102

Asia WGS

AF:

0.0950

AC:

328

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

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