rs11047912

Positions:

• chr12-25232976-T-C
• chr12-25232976-T-G

Variant summary

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

The ENST00000556131.2(KRAS):​c.*2230A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,188 control chromosomes in the GnomAD database, including 4,490 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 0.24 (4490 hom., cov: 32)
• Consequence: KRAS ENST00000556131.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_004985.5	c.112-5564A>G		intron_variant		ENST00000311936.8
KRAS	NM_033360.4	c.112-5564A>G		intron_variant		ENST00000256078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRAS	ENST00000256078.10	c.112-5564A>G		intron_variant		1	NM_033360.4	A1
KRAS	ENST00000311936.8	c.112-5564A>G		intron_variant		1	NM_004985.5	P4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35936 AN: 152070 Hom.: 4482 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.236 AC: 35962 AN: 152188 Hom.: 4490 Cov.: 32 AF XY: 0.231 AC XY: 17189 AN XY: 74424

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.259

Alfa AF: 0.267 Hom.: 3158

Bravo AF: 0.238

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.53

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: rs11047912; hg19: chr12-25385910;