chr12-25246039-G-A

Position:

• chr12-25246039-G-A

Variant summary

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

The NM_004985.5(KRAS):​c.-11-644C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 150,730 control chromosomes in the GnomAD database, including 2,844 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 0.19 (2844 hom., cov: 30)
• Consequence: KRAS NM_004985.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRAS	NM_004985.5	c.-11-644C>T		intron_variant		ENST00000311936.8	NP_004976.2
KRAS	NM_033360.4	c.-11-644C>T		intron_variant		ENST00000256078.10	NP_203524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000256078.10	c.-11-644C>T		intron_variant		1	NM_033360.4	ENSP00000256078	A1
KRAS	ENST00000311936.8	c.-11-644C>T		intron_variant		1	NM_004985.5	ENSP00000308495	P4

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28771 AN: 150608 Hom.: 2838 Cov.: 30

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.191 AC: 28789 AN: 150730 Hom.: 2844 Cov.: 30 AF XY: 0.187 AC XY: 13766 AN XY: 73444

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.201

Alfa AF: 0.0991 Hom.: 135

Bravo AF: 0.189

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
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: rs7309670; hg19: chr12-25398973;