12-25229252-T-G

Position:

• chr12-25229252-T-G

Variant summary

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

The ENST00000311936.8(KRAS):​c.112-1840A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 152,210 control chromosomes in the GnomAD database, including 393 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 0.062 (393 hom., cov: 32)
• Consequence: KRAS ENST00000311936.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRAS	NM_004985.5	c.112-1840A>C		intron_variant		ENST00000311936.8	NP_004976.2
KRAS	NM_033360.4	c.112-1840A>C		intron_variant		ENST00000256078.10	NP_203524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000256078.10	c.112-1840A>C		intron_variant		1	NM_033360.4	ENSP00000256078	A1
KRAS	ENST00000311936.8	c.112-1840A>C		intron_variant		1	NM_004985.5	ENSP00000308495	P4

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9397 AN: 152092 Hom.: 392 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.0941

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0933

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0618 AC: 9402 AN: 152210 Hom.: 393 Cov.: 32 AF XY: 0.0588 AC XY: 4378 AN XY: 74414

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.0788

Gnomad4 ASJ AF: 0.0941

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0197

Gnomad4 FIN AF: 0.0347

Gnomad4 NFE AF: 0.0933

Gnomad4 OTH AF: 0.0767

Alfa AF: 0.0653 Hom.: 64

Bravo AF: 0.0639

Asia WGS AF: 0.0120 AC: 43 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	15
DANN	Benign	0.82

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: rs17388148; hg19: chr12-25382186;