Variant chr12-25206293-A-T 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.*3502T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 208,276 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 88 hom., cov: 32)

Exomes 𝑓: 0.017 ( 13 hom. )

Consequence

KRAS
NM_004985.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.18

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=-0.47).

BP6

Variant 12-25206293-A-T is Benign according to our data. Variant chr12-25206293-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 308072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0854 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.*3502T>A		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.*3502T>A		3_prime_UTR_variant	5/5	1	NM_004985.5	ENSP00000308495.3		P01116-2

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3547

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0418

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.0600

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0922

Gnomad FIN

AF:

0.00414

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.0239

GnomAD4 exome

AF:

0.0169

AC:

946

AN:

56026

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

438

AN XY:

25952

show subpopulations

Gnomad4 AFR exome

AF:

0.0389

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0647

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0721

Gnomad4 FIN exome

AF:

0.00429

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0192

GnomAD4 genome

AF:

0.0234

AC:

3556

AN:

152250

Hom.:

Cov.:

AF XY:

0.0248

AC XY:

1846

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0419

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.0600

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0925

Gnomad4 FIN

AF:

0.00414

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0181

Hom.:

Bravo

AF:

0.0237

Asia WGS

AF:

0.0350

AC:

121

AN:

3470

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

-0.47

CADD

Benign

DANN

Benign

0.87

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