Variant rs397517040 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PP5_ModerateBP4BP7BS2

The NM_004985.5(KRAS):c.39C>T(p.Gly13Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

KRAS
NM_004985.5 synonymous

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1U:2

Conservation

PhyloP100: 2.58

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP5

Variant 12-25245346-G-A is Pathogenic according to our data. Variant chr12-25245346-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 45125.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26). . Strength limited to SUPPORTING due to the PP5.

BP7

Synonymous conserved (PhyloP=2.58 with no splicing effect.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRAS	NM_004985.5 linkuse as main transcript	c.39C>T	p.Gly13Gly	synonymous_variant	2/5	ENST00000311936.8	NP_004976.2	P01116-2A0A024RAV5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000311936.8 linkuse as main transcript	c.39C>T	p.Gly13Gly	synonymous_variant	2/5	1	NM_004985.5	ENSP00000308495.3		P01116-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249446

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460512

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726488

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Non-small cell lung carcinoma

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 12, 2011

DNA sequencing of KRAS identified the variants listed above. From this test, we are unable to determine if these variants occur on the same chromosome (in cis) or on different chromosomes (in trans; as listed above). The Gly13Val variant h as been reported in 1 lung adenocarcinoma that did not respond to TKI treatment (Marchetti 2009; COSMIC). The Gly13Gly variant has not been reported in a lung t umor, but has been seen in several other tumor sites, including pancreas and lar ge intestine (COSMIC). If the two variants occur on the same chromosome (in cis) , the resulting variant would be 38_39delinsTT (Gly13Val), which has been previo usly identified in 2 lung carcinomas (COSMIC). Somatic KRAS variants have been a ssociated with resistance to EGFR TKIs (Pao 2005). -

Prostate cancer, hereditary, 1

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Laboratory of Virology, Oncology, Biosciences and Environment, Faculty of Sciences and Techniques, Mohammedia- University Hassan II of Casablanca

Jul 29, 2022

- -

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over