rs11047919

chr12-25246187-A-Cchr12-25246187-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004985.5(KRAS):c.-11-792T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 148,304 control chromosomes in the GnomAD database, including 17,882 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (17882 hom., cov: 27)
• Consequence: KRAS NM_004985.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_004985.5	c.-11-792T>G		intron_variant		ENST00000311936.8
KRAS	NM_033360.4	c.-11-792T>G		intron_variant		ENST00000256078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRAS	ENST00000256078.10	c.-11-792T>G		intron_variant		1	NM_033360.4	A1
KRAS	ENST00000311936.8	c.-11-792T>G		intron_variant		1	NM_004985.5	P4

Frequencies

GnomAD3 genomes AF: 0.462 AC: 68507 AN: 148200 Hom.: 17879 Cov.: 27

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.480

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.462 AC: 68518 AN: 148304 Hom.: 17882 Cov.: 27 AF XY: 0.464 AC XY: 33323 AN XY: 71832

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.481

Alfa AF: 0.536 Hom.: 11136

Bravo AF: 0.452

Asia WGS AF: 0.655 AC: 2278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.1
Dann	Benign	0.49

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

Other links and lift over

dbSNP: rs11047919; hg19: chr12-25399121;