rs712

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_033360.4(KRAS):c.*298T>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_033360.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.46

Publications

93 publications found

Variant links:

COSMIC-nc: COSV55614059

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 was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 40467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRAS	NM_033360.4 link	c.*298T>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000256078.10	NP_203524.1
KRAS	NM_004985.5 link	c.*177T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000311936.8	NP_004976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000256078.10 link	c.*298T>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_033360.4	ENSP00000256078.5
KRAS	ENST00000311936.8 link	c.*177T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_004985.5	ENSP00000308495.3

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

African (AFR)

AF:

0.226

AC:

5597

AN:

24794

American (AMR)

AF:

0.504

AC:

6171

AN:

12240

Ashkenazi Jewish (ASJ)

AF:

0.639

AC:

10739

AN:

16804

East Asian (EAS)

AF:

0.796

AC:

23351

AN:

29322

South Asian (SAS)

AF:

0.656

AC:

29540

AN:

44998

European-Finnish (FIN)

AF:

0.558

AC:

16892

AN:

30290

Middle Eastern (MID)

AF:

0.558

AC:

1817

AN:

3254

European-Non Finnish (NFE)

AF:

0.538

AC:

526886

AN:

979646

Other (OTH)

AF:

0.554

AC:

26873

AN:

48534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

13846

27693

41539

55386

69232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16374

32748

49122

65496

81870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.468

AC:

71139

AN:

151898

Hom.:

18345

Cov.:

AF XY:

0.474

AC XY:

35183

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.244

AC:

10100

AN:

41464

American (AMR)

AF:

0.492

AC:

7507

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.625

AC:

2166

AN:

3468

East Asian (EAS)

AF:

0.800

AC:

4144

AN:

5178

South Asian (SAS)

AF:

0.668

AC:

3208

AN:

4802

European-Finnish (FIN)

AF:

0.542

AC:

5690

AN:

10500

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.541

AC:

36777

AN:

67920

Other (OTH)

AF:

0.486

AC:

1027

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1788

3575

5363

7150

8938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.495

Hom.:

2786

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24552817, 25961464, 26535719) -

Noonan syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Noonan syndrome and Noonan-related syndrome

Benign:1

Jul 13, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

RASopathy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over