1-114716959-T-C

Variant names:

• chr1-114716959-T-C
• rs6694035
• NM_001007553.3:c.*1210A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001007553.3(CSDE1):​c.*1210A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0083 in 152,800 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (0 hom.)
• Consequence: CSDE1 NM_001007553.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.29

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 1-114716959-T-C is Benign according to our data. Variant chr1-114716959-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1202429.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00832 (1268/152370) while in subpopulation NFE AF= 0.0143 (972/68042). AF 95% confidence interval is 0.0135. There are 7 homozygotes in gnomad4. There are 561 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1268 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSDE1	NM_001007553.3	c.*1210A>G		3_prime_UTR_variant	Exon 20 of 20	ENST00000358528.9	NP_001007554.1
NRAS	NM_002524.5	c.-319A>G		upstream_gene_variant		ENST00000369535.5	NP_002515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSDE1	ENST00000358528	c.*1210A>G		3_prime_UTR_variant	Exon 20 of 20	1	NM_001007553.3	ENSP00000351329.4
NRAS	ENST00000369535.5	c.-319A>G		upstream_gene_variant		1	NM_002524.5	ENSP00000358548.4

Frequencies

GnomAD3 genomes AF: 0.00833 AC: 1268 AN: 152252 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00562

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00518

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.00863

GnomAD4 exome AF: 0.00233 AC: 1 AN: 430 Hom.: 0 Cov.: 0 AF XY: 0.00388 AC XY: 1 AN XY: 258

Gnomad4 FIN exome AF: 0.00244

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00832 AC: 1268 AN: 152370 Hom.: 7 Cov.: 33 AF XY: 0.00753 AC XY: 561 AN XY: 74516

Gnomad4 AFR AF: 0.00257

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00518

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.00854

Alfa AF: 0.00497 Hom.: 0

Bravo AF: 0.00791

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 23, 2018

GeneDx

Significance: Likely 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	-0.63
CADD	Benign	18
DANN	Benign	0.85

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

Other links and lift over

dbSNP: rs6694035; hg19: chr1-115259580;