NM_001007553.3:c.*1191C>A

Variant names:

• chr1-114716978-G-T
• rs8453
• NM_001007553.3:c.*1191C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.02
• Publications: 30 publications found

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]

NRAS Gene-Disease associations (from GenCC):

• Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Noonan syndrome 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• cardiofaciocutaneous syndrome

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: ClinGen, Genomics England PanelApp
• Costello syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• Noonan syndrome with multiple lentigines

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• Noonan syndrome-like disorder with loose anagen hair

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSDE1	NM_001007553.3	MANE Select	c.*1191C>A		3_prime_UTR	Exon 20 of 20	NP_001007554.1	O75534-1
	CSDE1	NM_001242891.2		c.*1191C>A		3_prime_UTR	Exon 21 of 21	NP_001229820.1	O75534-4
	CSDE1	NM_001130523.3		c.*1191C>A		3_prime_UTR	Exon 20 of 20	NP_001123995.1	O75534-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSDE1	ENST00000358528.9	TSL:1 MANE Select	c.*1191C>A		3_prime_UTR	Exon 20 of 20	ENSP00000351329.4	O75534-1
	CSDE1	ENST00000438362.7	TSL:1	c.*1191C>A		3_prime_UTR	Exon 21 of 21	ENSP00000407724.3	O75534-1
	CSDE1	ENST00000339438.10	TSL:1	c.*1191C>A		3_prime_UTR	Exon 19 of 19	ENSP00000342408.6	O75534-2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16932 AN: 152166 Hom.: 1201 Cov.: 33

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: 78 AN: 442 Hom.: 9 Cov.: 0 AF XY: 0.177 AC XY: 46 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.181 AC: 75 AN: 414

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0909 AC: 2 AN: 22

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.111 AC: 16931 AN: 152284 Hom.: 1201 Cov.: 33 AF XY: 0.111 AC XY: 8257 AN XY: 74456

African (AFR) AF: 0.0256 AC: 1066 AN: 41566

American (AMR) AF: 0.128 AC: 1959 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3470

East Asian (EAS) AF: 0.0900 AC: 467 AN: 5188

South Asian (SAS) AF: 0.0754 AC: 364 AN: 4826

European-Finnish (FIN) AF: 0.179 AC: 1899 AN: 10604

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10521 AN: 68008

Other (OTH) AF: 0.0875 AC: 185 AN: 2114

Alfa AF: 0.138 Hom.: 4673

Bravo AF: 0.102

Asia WGS AF: 0.0950 AC: 328 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.91
PhyloP100		6.0
PromoterAI		-0.044	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8453; hg19: chr1-115259599;