Variant rs712 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.*177T>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 0.536 in 1,341,780 control chromosomes in the GnomAD database, including 198,236 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 ( 18345 hom., cov: 31)

Exomes 𝑓: 0.54 ( 179891 hom. )

Consequence

KRAS
NM_004985.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.46

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=-0.31).

BP6

Variant 12-25209618-A-C is Benign according to our data. Variant chr12-25209618-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 40467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-25209618-A-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.*177T>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.*177T>G		3_prime_UTR_variant	5/5	1	NM_004985.5	ENSP00000308495.3		P01116-2

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71110

AN:

151780

Hom.:

18340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.400

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.625

Gnomad EAS

AF:

0.801

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.541

Gnomad OTH

AF:

0.485

GnomAD4 exome

AF:

0.544

AC:

647866

AN:

1189882

Hom.:

179891

Cov.:

AF XY:

0.547

AC XY:

313066

AN XY:

572148

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.504

Gnomad4 ASJ exome

AF:

0.639

Gnomad4 EAS exome

AF:

0.796

Gnomad4 SAS exome

AF:

0.656

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.538

Gnomad4 OTH exome

AF:

0.554

GnomAD4 genome

AF:

0.468

AC:

71139

AN:

151898

Hom.:

18345

Cov.:

AF XY:

0.474

AC XY:

35183

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.492

Gnomad4 ASJ

AF:

0.625

Gnomad4 EAS

AF:

0.800

Gnomad4 SAS

AF:

0.668

Gnomad4 FIN

AF:

0.542

Gnomad4 NFE

AF:

0.541

Gnomad4 OTH

AF:

0.486

Alfa

AF:

0.504

Hom.:

2755

Bravo

AF:

0.455

Asia WGS

AF:

0.681

AC:

2365

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 24552817, 25961464, 26535719) -

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

- -

RASopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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