1-114705128-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002524.5(NRAS):c.*2965del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,978 control chromosomes in the GnomAD database, including 3,575 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3575 hom., cov: 27)
  • Failed GnomAD Quality Control
• Consequence: NRAS NM_002524.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.306

Genes affected

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 -10 ACMG points.

• BP6: Variant 1-114705128-TA-T is Benign according to our data. Variant chr1-114705128-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 291946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRAS	NM_002524.5	c.*2965del		3_prime_UTR_variant	7/7	ENST00000369535.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRAS	ENST00000369535.5	c.*2965del		3_prime_UTR_variant	7/7	1	NM_002524.5	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30801 AN: 151860 Hom.: 3575 Cov.: 27

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.0228

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.209

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.203 AC: 30810 AN: 151978 Hom.: 3575 Cov.: 27 AF XY: 0.201 AC XY: 14948 AN XY: 74250

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.0228

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.207

Alfa AF: 0.120 Hom.: 225

Bravo AF: 0.187

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Noonan syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs61652108; hg19: chr1-115247749;