Variant chr12-25205716-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.*4079T>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 0.519 in 222,762 control chromosomes in the GnomAD database, including 31,530 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 ( 19367 hom., cov: 31)

Exomes 𝑓: 0.58 ( 12163 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: 2.02

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=-0.82).

BP6

Variant 12-25205716-A-T is Benign according to our data. Variant chr12-25205716-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 308059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 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.*4079T>A		3_prime_UTR_variant	5/5	ENST00000311936.8	NP_004976.2
KRAS	NM_033360.4 linkuse as main transcript	c.*4200T>A		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.*4200T>A		3_prime_UTR_variant	6/6	1	NM_033360.4	ENSP00000256078	A1	P01116-1
KRAS	ENST00000311936.8 linkuse as main transcript	c.*4079T>A		3_prime_UTR_variant	5/5	1	NM_004985.5	ENSP00000308495	P4	P01116-2

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74764

AN:

151734

Hom.:

19356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.624

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.541

Gnomad OTH

AF:

0.506

GnomAD4 exome

AF:

0.576

AC:

40809

AN:

70910

Hom.:

12163

Cov.:

AF XY:

0.577

AC XY:

18923

AN XY:

32786

show subpopulations

Gnomad4 AFR exome

AF:

0.335

Gnomad4 AMR exome

AF:

0.498

Gnomad4 ASJ exome

AF:

0.642

Gnomad4 EAS exome

AF:

0.792

Gnomad4 SAS exome

AF:

0.664

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.543

Gnomad4 OTH exome

AF:

0.554

GnomAD4 genome

AF:

0.493

AC:

74805

AN:

151852

Hom.:

19367

Cov.:

AF XY:

0.498

AC XY:

36962

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.328

Gnomad4 AMR

AF:

0.500

Gnomad4 ASJ

AF:

0.624

Gnomad4 EAS

AF:

0.800

Gnomad4 SAS

AF:

0.668

Gnomad4 FIN

AF:

0.544

Gnomad4 NFE

AF:

0.541

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.516

Hom.:

2615

Bravo

AF:

0.482

Asia WGS

AF:

0.690

AC:

2401

AN:

3478

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

Dec 23, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.64

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