Variant chr12-25207290-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004985.5(KRAS):c.*2505T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 195,932 control chromosomes in the GnomAD database, including 528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 390 hom., cov: 31)

Exomes 𝑓: 0.073 ( 138 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: 0.836

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-25207290-A-C is Benign according to our data. Variant chr12-25207290-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 308084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-25207290-A-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_004985.5 linkuse as main transcript	c.*2505T>G		3_prime_UTR_variant	5/5	ENST00000311936.8
KRAS	NM_033360.4 linkuse as main transcript	c.*2626T>G		3_prime_UTR_variant	6/6	ENST00000256078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRAS	ENST00000256078.10 linkuse as main transcript	c.*2626T>G		3_prime_UTR_variant	6/6	1	NM_033360.4	A1	P01116-1
KRAS	ENST00000311936.8 linkuse as main transcript	c.*2505T>G		3_prime_UTR_variant	5/5	1	NM_004985.5	P4	P01116-2

Frequencies

GnomAD3 genomes

AF:

0.0617

AC:

9391

AN:

152092

Hom.:

389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0790

Gnomad ASJ

AF:

0.0923

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0189

Gnomad FIN

AF:

0.0348

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0932

Gnomad OTH

AF:

0.0773

GnomAD4 exome

AF:

0.0726

AC:

3176

AN:

43722

Hom.:

138

Cov.:

AF XY:

0.0744

AC XY:

1516

AN XY:

20390

show subpopulations

Gnomad4 AFR exome

AF:

0.0251

Gnomad4 AMR exome

AF:

0.0706

Gnomad4 ASJ exome

AF:

0.0966

Gnomad4 EAS exome

AF:

0.000137

Gnomad4 SAS exome

AF:

0.00847

Gnomad4 FIN exome

AF:

0.0833

Gnomad4 NFE exome

AF:

0.0936

Gnomad4 OTH exome

AF:

0.0791

GnomAD4 genome

AF:

0.0617

AC:

9396

AN:

152210

Hom.:

390

Cov.:

AF XY:

0.0588

AC XY:

4375

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0190

Gnomad4 AMR

AF:

0.0789

Gnomad4 ASJ

AF:

0.0923

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0195

Gnomad4 FIN

AF:

0.0348

Gnomad4 NFE

AF:

0.0932

Gnomad4 OTH

AF:

0.0764

Alfa

AF:

0.0702

Hom.:

Bravo

AF:

0.0638

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Noonan syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

RASopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Noonan syndrome and Noonan-related syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Nov 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.2

DANN

Benign

0.73

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