chr12-25239509-C-T

Position:

• chr12-25239509-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.111+5765G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,962 control chromosomes in the GnomAD database, including 11,825 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 0.39 (11825 hom., cov: 32)
• Consequence: KRAS NM_004985.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRAS	NM_004985.5	c.111+5765G>A		intron_variant		ENST00000311936.8	NP_004976.2
KRAS	NM_033360.4	c.111+5765G>A		intron_variant		ENST00000256078.10	NP_203524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000256078.10	c.111+5765G>A		intron_variant		1	NM_033360.4	ENSP00000256078	A1
KRAS	ENST00000311936.8	c.111+5765G>A		intron_variant		1	NM_004985.5	ENSP00000308495	P4

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59479 AN: 151844 Hom.: 11801 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.392 AC: 59549 AN: 151962 Hom.: 11825 Cov.: 32 AF XY: 0.392 AC XY: 29073 AN XY: 74256

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.372

Alfa AF: 0.392 Hom.: 1972

Bravo AF: 0.392

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.29

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: rs10505980; hg19: chr12-25392443;