rs190218019

Variant names:

• chr12-25250917-G-A
• rs190218019
• NM_004985.5:c.-178C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-25250917-G-A
• chr12-25250917-G-C
• chr12-25250917-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004985.5(KRAS):​c.-178C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRAS NM_004985.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• Publications: 3 publications found

Genes affected

KRAS (HGNC:6407): (KRAS proto-oncogene, GTPase) This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]

KRAS Gene-Disease associations (from GenCC):

• cardiofaciocutaneous syndrome 2

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

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Noonan syndrome 3

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

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen
• linear nevus sebaceous syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Costello syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRAS	NM_004985.5	c.-178C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	ENST00000311936.8	NP_004976.2
KRAS	NM_004985.5	c.-178C>T		5_prime_UTR_variant	Exon 1 of 5	ENST00000311936.8	NP_004976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000311936.8	c.-178C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	1	NM_004985.5	ENSP00000308495.3
KRAS	ENST00000311936.8	c.-178C>T		5_prime_UTR_variant	Exon 1 of 5	1	NM_004985.5	ENSP00000308495.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 98888 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 52902

African (AFR) AF: 0.00 AC: 0 AN: 3272

American (AMR) AF: 0.00 AC: 0 AN: 2146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4350

East Asian (EAS) AF: 0.00 AC: 0 AN: 10866

South Asian (SAS) AF: 0.00 AC: 0 AN: 4008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 534

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65326

Other (OTH) AF: 0.00 AC: 0 AN: 6878

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	0.98
PhyloP100		0.49
PromoterAI		-0.056	Neutral
Mutation Taster		=299/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs190218019; hg19: chr12-25403851;