rs4623993

Positions:

• chr12-25232494-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.112-5082G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,914 control chromosomes in the GnomAD database, including 2,852 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 (2852 hom., cov: 32)
• Consequence: KRAS NM_004985.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRAS	NM_004985.5	c.112-5082G>A		intron_variant		ENST00000311936.8	NP_004976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000311936.8	c.112-5082G>A		intron_variant		1	NM_004985.5	ENSP00000308495.3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28201 AN: 151798 Hom.: 2838 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0935

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.186 AC: 28244 AN: 151914 Hom.: 2852 Cov.: 32 AF XY: 0.190 AC XY: 14075 AN XY: 74244

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.0935

Gnomad4 EAS AF: 0.0976

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.155

Alfa AF: 0.172 Hom.: 406

Bravo AF: 0.186

Asia WGS AF: 0.0950 AC: 330 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.86
DANN	Benign	0.20

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: rs4623993; hg19: chr12-25385428;