chr12-25239348-C-T

Position:

• chr12-25239348-C-T

Variant summary

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

The NM_004985.5(KRAS):​c.111+5926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,024 control chromosomes in the GnomAD database, including 13,057 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 0.38 (13057 hom., cov: 32)
• Consequence: KRAS NM_004985.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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 = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRAS	NM_004985.5	c.111+5926G>A		intron_variant		ENST00000311936.8	NP_004976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000311936.8	c.111+5926G>A		intron_variant		1	NM_004985.5	ENSP00000308495.3

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57970 AN: 151906 Hom.: 13053 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.381 AC: 57981 AN: 152024 Hom.: 13057 Cov.: 32 AF XY: 0.386 AC XY: 28721 AN XY: 74318

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.401

Alfa AF: 0.447 Hom.: 20163

Bravo AF: 0.375

Asia WGS AF: 0.593 AC: 2057 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.24

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: rs10842514; hg19: chr12-25392282;