Variant rs199716819 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004985.5(KRAS):c.111+46T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,558,012 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 7 hom. )

Consequence

KRAS
NM_004985.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.144

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-25245228-A-C is Benign according to our data. Variant chr12-25245228-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 259601.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00147 (224/152380) while in subpopulation SAS AF= 0.00269 (13/4832). AF 95% confidence interval is 0.00223. There are 0 homozygotes in gnomad4. There are 103 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 224 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_004985.5 linkuse as main transcript	c.111+46T>G		intron_variant		ENST00000311936.8
KRAS	NM_033360.4 linkuse as main transcript	c.111+46T>G		intron_variant		ENST00000256078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRAS	ENST00000256078.10 linkuse as main transcript	c.111+46T>G		intron_variant		1	NM_033360.4	A1	P01116-1
KRAS	ENST00000311936.8 linkuse as main transcript	c.111+46T>G		intron_variant		1	NM_004985.5	P4	P01116-2

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

224

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00172

AC:

314

AN:

183066

Hom.:

AF XY:

0.00172

AC XY:

168

AN XY:

97554

show subpopulations

Gnomad AFR exome

AF:

0.000177

Gnomad AMR exome

AF:

0.000508

Gnomad ASJ exome

AF:

0.000883

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00189

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.00273

Gnomad OTH exome

AF:

0.00221

GnomAD4 exome

AF:

0.00248

AC:

3492

AN:

1405632

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

1779

AN XY:

695682

show subpopulations

Gnomad4 AFR exome

AF:

0.000251

Gnomad4 AMR exome

AF:

0.000444

Gnomad4 ASJ exome

AF:

0.00106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00229

Gnomad4 FIN exome

AF:

0.00202

Gnomad4 NFE exome

AF:

0.00283

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152380

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

103

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000288

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00254

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00179

Hom.:

Bravo

AF:

0.00133

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.72

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