rs11047917

Variant names:

• chr12-25243642-C-T
• rs11047917
• NM_033360.4:c.111+1632G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004985.5(KRAS):​c.111+1632G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 152,248 control chromosomes in the GnomAD database, including 273 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. The gene KRAS is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.050 (273 hom., cov: 32)
• Consequence: KRAS NM_004985.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 9 publications found

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]

KRAS Gene-Disease associations (from GenCC):

• cardiofaciocutaneous syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Noonan syndrome 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
• cardiofaciocutaneous syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen
• linear nevus sebaceous syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Costello syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome with multiple lentigines

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome-like disorder with loose anagen hair

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Specifications for KRAS are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0918 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004985.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRAS	NM_033360.4	MANE Plus Clinical	c.111+1632G>A		intron	N/A	NP_203524.1	P01116-1
	KRAS	NM_004985.5	MANE Select	c.111+1632G>A		intron	N/A	NP_004976.2
	KRAS	NM_001369786.1		c.111+1632G>A		intron	N/A	NP_001356715.1	P01116-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRAS	ENST00000256078.10	TSL:1 MANE Plus Clinical	c.111+1632G>A		intron	N/A	ENSP00000256078.5	P01116-1
	KRAS	ENST00000311936.8	TSL:1 MANE Select	c.111+1632G>A		intron	N/A	ENSP00000308495.3	P01116-2
	KRAS	ENST00000556131.2	TSL:1	c.111+1632G>A		intron	N/A	ENSP00000451856.1	G3V4K2

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7536 AN: 152130 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0870

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.0986

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0496 AC: 7551 AN: 152248 Hom.: 273 Cov.: 32 AF XY: 0.0502 AC XY: 3733 AN XY: 74434

African (AFR) AF: 0.0133 AC: 553 AN: 41558

American (AMR) AF: 0.0869 AC: 1329 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3472

East Asian (EAS) AF: 0.0988 AC: 513 AN: 5190

South Asian (SAS) AF: 0.0790 AC: 381 AN: 4820

European-Finnish (FIN) AF: 0.0318 AC: 337 AN: 10602

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0612 AC: 4160 AN: 68000

Other (OTH) AF: 0.0559 AC: 118 AN: 2112

Alfa AF: 0.0578 Hom.: 285

Bravo AF: 0.0507

Asia WGS AF: 0.115 AC: 400 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11047917; hg19: chr12-25396576;