Variant rs9266 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_004985.5(KRAS):c.*512T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 644,948 control chromosomes in the GnomAD database, including 100,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19406 hom., cov: 31)

Exomes 𝑓: 0.57 ( 81507 hom. )

Consequence

KRAS
NM_004985.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.472

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:

ETFRF1 (HGNC:27052): (electron transfer flavoprotein regulatory factor 1) Involved in respiratory electron transport chain. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ETFRF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 12-25209283-A-G is Benign according to our data. Variant chr12-25209283-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 308118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-25209283-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRAS	NM_004985.5 linkuse as main transcript	c.*512T>C		3_prime_UTR_variant	5/5	ENST00000311936.8	NP_004976.2
KRAS	NM_033360.4 linkuse as main transcript	c.*633T>C		3_prime_UTR_variant	6/6	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.*633T>C		3_prime_UTR_variant	6/6	1	NM_033360.4	ENSP00000256078	A1	P01116-1
KRAS	ENST00000311936.8 linkuse as main transcript	c.*512T>C		3_prime_UTR_variant	5/5	1	NM_004985.5	ENSP00000308495	P4	P01116-2

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74841

AN:

151788

Hom.:

19394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.624

Gnomad EAS

AF:

0.801

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.506

GnomAD3 exomes

AF:

0.581

AC:

61555

AN:

106036

Hom.:

18269

AF XY:

0.584

AC XY:

34276

AN XY:

58664

show subpopulations

Gnomad AFR exome

AF:

0.324

Gnomad AMR exome

AF:

0.546

Gnomad ASJ exome

AF:

0.632

Gnomad EAS exome

AF:

0.806

Gnomad SAS exome

AF:

0.665

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.542

Gnomad OTH exome

AF:

0.558

GnomAD4 exome

AF:

0.567

AC:

279771

AN:

493042

Hom.:

81507

Cov.:

AF XY:

0.572

AC XY:

152847

AN XY:

267114

show subpopulations

Gnomad4 AFR exome

AF:

0.328

Gnomad4 AMR exome

AF:

0.530

Gnomad4 ASJ exome

AF:

0.639

Gnomad4 EAS exome

AF:

0.797

Gnomad4 SAS exome

AF:

0.655

Gnomad4 FIN exome

AF:

0.563

Gnomad4 NFE exome

AF:

0.541

Gnomad4 OTH exome

AF:

0.554

GnomAD4 genome

AF:

0.493

AC:

74883

AN:

151906

Hom.:

19406

Cov.:

AF XY:

0.499

AC XY:

37018

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.328

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.624

Gnomad4 EAS

AF:

0.801

Gnomad4 SAS

AF:

0.668

Gnomad4 FIN

AF:

0.543

Gnomad4 NFE

AF:

0.542

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.541

Hom.:

46975

Bravo

AF:

0.482

Asia WGS

AF:

0.691

AC:

2401

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Noonan syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Noonan syndrome and Noonan-related syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.86

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