dbSNP rs886049179: KRAS:c.*4036A>G (chr12-25205880-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004985.5(KRAS):c.*3915A>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 0.000216 in 217,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

KRAS
NM_004985.5 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.779

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 12-25205880-T-C is Benign according to our data. Variant chr12-25205880-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 308063.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000158 (24/152310) while in subpopulation EAS AF = 0.00366 (19/5194). AF 95% confidence interval is 0.00239. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 24 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004985.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KRAS	NM_033360.4	MANE Plus Clinical	c.*4036A>G	3_prime_UTR	Exon 6 of 6	NP_203524.1	P01116-1
KRAS	NM_004985.5	MANE Select	c.*3915A>G	3_prime_UTR	Exon 5 of 5	NP_004976.2
KRAS	NM_001369786.1		c.*4036A>G	3_prime_UTR	Exon 6 of 6	NP_001356715.1	P01116-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KRAS	ENST00000256078.10	TSL:1 MANE Plus Clinical	c.*4036A>G	3_prime_UTR	Exon 6 of 6	ENSP00000256078.5	P01116-1
KRAS	ENST00000311936.8	TSL:1 MANE Select	c.*3915A>G	3_prime_UTR	Exon 5 of 5	ENSP00000308495.3	P01116-2
KRAS	ENST00000685328.1		c.*3915A>G	3_prime_UTR	Exon 5 of 5	ENSP00000508921.1	P01116-2

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00365

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000354

AC:

AN:

64990

Hom.:

Cov.:

AF XY:

0.000397

AC XY:

AN XY:

30224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3114

American (AMR)

AF:

0.00

AC:

AN:

1956

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4120

East Asian (EAS)

AF:

0.00237

AC:

AN:

9270

South Asian (SAS)

AF:

0.00

AC:

AN:

566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

402

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

40022

Other (OTH)

AF:

0.000182

AC:

AN:

5496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000158

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41572

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00366

AC:

AN:

5194

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000174

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Noonan syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.8

(source)

DANN

Benign

0.71

PhyloP100

0.78

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over