rs183538580

Variant names:

• chr19-49635633-C-G
• rs183538580
• NM_006270.5:c.600G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-49635633-C-G
• chr19-49635633-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006270.5(RRAS):​c.600G>C​(p.Pro200Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000773 in 1,294,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P200P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: RRAS NM_006270.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 0 publications found

Genes affected

RRAS (HGNC:10447): (RAS related) The protein encoded by this gene is a small GTPase involved in diverse processes including angiogenesis, vascular homeostasis and regeneration, cell adhesion, and neuronal axon guidance. Mutations in this gene are found in many invasive cancers. [provided by RefSeq, Jul 2015]

RRAS Gene-Disease associations (from GenCC):

• Noonan syndrome and Noonan-related syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P
• Noonan syndrome

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.322 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRAS	NM_006270.5	c.600G>C	p.Pro200Pro	synonymous_variant	Exon 6 of 6	ENST00000246792.4	NP_006261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRAS	ENST00000246792.4	c.600G>C	p.Pro200Pro	synonymous_variant	Exon 6 of 6	1	NM_006270.5	ENSP00000246792.2
RRAS	ENST00000601532.1	n.*179G>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.73e-7 AC: 1 AN: 1294062 Hom.: 0 Cov.: 31 AF XY: 0.00000158 AC XY: 1 AN XY: 632646

African (AFR) AF: 0.00 AC: 0 AN: 27880

American (AMR) AF: 0.00 AC: 0 AN: 27198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18550

East Asian (EAS) AF: 0.00 AC: 0 AN: 33846

South Asian (SAS) AF: 0.0000162 AC: 1 AN: 61874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4962

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1019896

Other (OTH) AF: 0.00 AC: 0 AN: 52146

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.2
DANN	Benign	0.58
PhyloP100		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs183538580; hg19: chr19-50138890;