Variant 12-25206907-T-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.*2888A>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 0.498 in 201,246 control chromosomes in the GnomAD database, including 27,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18538 hom., cov: 32)

Exomes 𝑓: 0.57 ( 8470 hom. )

Consequence

KRAS
NM_004985.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0860

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=-0.98).

BP6

Variant 12-25206907-T-C is Benign according to our data. Variant chr12-25206907-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 308082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-25206907-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 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.*2888A>G		3_prime_UTR_variant	5/5	ENST00000311936.8	NP_004976.2	P01116-2A0A024RAV5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000311936 linkuse as main transcript	c.*2888A>G		3_prime_UTR_variant	5/5	1	NM_004985.5	ENSP00000308495.3		P01116-2

Frequencies

GnomAD3 genomes

AF:

0.473

AC:

71832

AN:

151930

Hom.:

18531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.624

Gnomad EAS

AF:

0.801

Gnomad SAS

AF:

0.668

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.541

Gnomad OTH

AF:

0.487

GnomAD4 exome

AF:

0.574

AC:

28261

AN:

49198

Hom.:

8470

Cov.:

AF XY:

0.577

AC XY:

13199

AN XY:

22860

show subpopulations

Gnomad4 AFR exome

AF:

0.261

Gnomad4 AMR exome

AF:

0.498

Gnomad4 ASJ exome

AF:

0.631

Gnomad4 EAS exome

AF:

0.791

Gnomad4 SAS exome

AF:

0.690

Gnomad4 FIN exome

AF:

0.462

Gnomad4 NFE exome

AF:

0.541

Gnomad4 OTH exome

AF:

0.541

GnomAD4 genome

AF:

0.473

AC:

71865

AN:

152048

Hom.:

18538

Cov.:

AF XY:

0.479

AC XY:

35579

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.494

Gnomad4 ASJ

AF:

0.624

Gnomad4 EAS

AF:

0.801

Gnomad4 SAS

AF:

0.667

Gnomad4 FIN

AF:

0.544

Gnomad4 NFE

AF:

0.541

Gnomad4 OTH

AF:

0.488

Alfa

AF:

0.523

Hom.:

15321

Bravo

AF:

0.459

Asia WGS

AF:

0.688

AC:

2391

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.98

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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