12-25236573-A-G

Position:

• chr12-25236573-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.111+8701T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 151,752 control chromosomes in the GnomAD database, including 68,133 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 0.95 (68133 hom., cov: 28)
• Consequence: KRAS NM_004985.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRAS	NM_004985.5	c.111+8701T>C		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+8701T>C		intron_variant		1	NM_004985.5	ENSP00000308495.3

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143365 AN: 151634 Hom.: 68077 Cov.: 28

Gnomad AFR AF: 0.854

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.951

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

GnomAD4 genome AF: 0.946 AC: 143482 AN: 151752 Hom.: 68133 Cov.: 28 AF XY: 0.946 AC XY: 70157 AN XY: 74154

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.969

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.907

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.986

Gnomad4 OTH AF: 0.951

Alfa AF: 0.967 Hom.: 20268

Bravo AF: 0.940

Asia WGS AF: 0.960 AC: 3338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.76

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: rs4495968; hg19: chr12-25389507;