Variant 12-25250767-G-GGAGCCGCTGAGCCTCTGGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_004985.5(KRAS):c.-29_-28insGGCCAGAGGCTCAGCGGCTC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000594 in 201,926 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 0 hom. )

Consequence

KRAS
NM_004985.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.671

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-25250767-G-GGAGCCGCTGAGCCTCTGGCC is Benign according to our data. Variant chr12-25250767-G-GGAGCCGCTGAGCCTCTGGCC is described in ClinVar as [Likely_benign]. Clinvar id is 177929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00058 (88/151840) while in subpopulation NFE AF= 0.00109 (74/67906). AF 95% confidence interval is 0.00089. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 88 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRAS	NM_004985.5 linkuse as main transcript	c.-29_-28insGGCCAGAGGCTCAGCGGCTC		5_prime_UTR_variant	1/5	ENST00000311936.8	NP_004976.2
KRAS	NM_033360.4 linkuse as main transcript	c.-29_-28insGGCCAGAGGCTCAGCGGCTC		5_prime_UTR_variant	1/6	ENST00000256078.10	NP_203524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000256078.10 linkuse as main transcript	c.-29_-28insGGCCAGAGGCTCAGCGGCTC		5_prime_UTR_variant	1/6	1	NM_033360.4	ENSP00000256078	A1	P01116-1
KRAS	ENST00000311936.8 linkuse as main transcript	c.-29_-28insGGCCAGAGGCTCAGCGGCTC		5_prime_UTR_variant	1/5	1	NM_004985.5	ENSP00000308495	P4	P01116-2

Frequencies

GnomAD3 genomes

AF:

0.000580

AC:

AN:

151840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.000639

AC:

AN:

50086

Hom.:

Cov.:

AF XY:

0.000654

AC XY:

AN XY:

24466

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000978

Gnomad4 OTH exome

AF:

0.000524

GnomAD4 genome

AF:

0.000580

AC:

AN:

151840

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.000242

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000843

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 17, 2012

-48_-29dup in the 5'UTR of exon 1 of KRAS: The -48_-29dup variant in the KRAS 5' UTR has not been previously reported in the literature. We have identified this variant in one proband and a reportedly unaffected parent in our laboratory. Th e 5' UTR plays a role in the regulation of gene expression and variants in this region have been shown to alter protein translation (Mendell 2001, Scheper 2007) . This type of variant has not been previously reported in an individual with a Noonan spectrum disorder. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 23, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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