rs12305513

Positions:

• chr12-25212289-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.451-2378T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,228 control chromosomes in the GnomAD database, including 2,734 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 0.15 (2734 hom., cov: 32)
• Consequence: KRAS NM_004985.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_004985.5	c.451-2378T>C		intron_variant		ENST00000311936.8
KRAS	NM_033360.4	c.*5-2378T>C		intron_variant		ENST00000256078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRAS	ENST00000256078.10	c.*5-2378T>C		intron_variant		1	NM_033360.4	A1
KRAS	ENST00000311936.8	c.451-2378T>C		intron_variant		1	NM_004985.5	P4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23556 AN: 152110 Hom.: 2722 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0225

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.155 AC: 23589 AN: 152228 Hom.: 2734 Cov.: 32 AF XY: 0.148 AC XY: 11021 AN XY: 74450

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.0348

Gnomad4 NFE AF: 0.0975

Gnomad4 OTH AF: 0.149

Alfa AF: 0.112 Hom.: 1125

Bravo AF: 0.169

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.77

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: rs12305513; hg19: chr12-25365223;