rs12579073

chr12-25222865-C-Achr12-25222865-C-Gchr12-25222865-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+2749G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,934 control chromosomes in the GnomAD database, including 16,977 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 0.45 (16977 hom., cov: 32)
• Consequence: KRAS NM_004985.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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 = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_004985.5	c.450+2749G>T		intron_variant		ENST00000311936.8
KRAS	NM_033360.4	c.450+2749G>T		intron_variant		ENST00000256078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRAS	ENST00000256078.10	c.450+2749G>T		intron_variant		1	NM_033360.4	A1
KRAS	ENST00000311936.8	c.450+2749G>T		intron_variant		1	NM_004985.5	P4

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67619 AN: 151816 Hom.: 16975 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.445 AC: 67639 AN: 151934 Hom.: 16977 Cov.: 32 AF XY: 0.450 AC XY: 33391 AN XY: 74252

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.463

Alfa AF: 0.508 Hom.: 24251

Bravo AF: 0.431

Asia WGS AF: 0.649 AC: 2256 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.049
Dann	Benign	0.51

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: rs12579073; hg19: chr12-25375799;