12-25218528-C-T

Position:

• chr12-25218528-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.450+7086G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,710 control chromosomes in the GnomAD database, including 4,463 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 0.24 (4463 hom., cov: 31)
• Consequence: KRAS NM_004985.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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]

LOC124902899 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRAS	NM_004985.5	c.450+7086G>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.450+7086G>A		intron_variant		1	NM_004985.5	ENSP00000308495.3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36301 AN: 151590 Hom.: 4455 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.239 AC: 36329 AN: 151710 Hom.: 4463 Cov.: 31 AF XY: 0.240 AC XY: 17790 AN XY: 74128

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.233

Alfa AF: 0.211 Hom.: 1296

Bravo AF: 0.241

Asia WGS AF: 0.105 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.55

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: rs10842508; hg19: chr12-25371462;