12-25236286-A-G

Position:

• chr12-25236286-A-G

Variant summary

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

The NM_004985.5(KRAS):​c.112-8874T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 152,280 control chromosomes in the GnomAD database, including 275 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 0.050 (275 hom., cov: 31)
• Consequence: KRAS NM_004985.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.097 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_004985.5	c.112-8874T>C		intron_variant		ENST00000311936.8
KRAS	NM_033360.4	c.112-8874T>C		intron_variant		ENST00000256078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRAS	ENST00000256078.10	c.112-8874T>C		intron_variant		1	NM_033360.4	A1
KRAS	ENST00000311936.8	c.112-8874T>C		intron_variant		1	NM_004985.5	P4

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7596 AN: 152162 Hom.: 270 Cov.: 31

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0794

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0613

Gnomad OTH AF: 0.0521

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

GnomAD4 genome AF: 0.0500 AC: 7611 AN: 152280 Hom.: 275 Cov.: 31 AF XY: 0.0506 AC XY: 3766 AN XY: 74464

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.0878

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0799

Gnomad4 FIN AF: 0.0320

Gnomad4 NFE AF: 0.0613

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0593 Hom.: 173

Bravo AF: 0.0512

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.69

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: rs17388587; hg19: chr12-25389220;