rs397517035

Variant names:

• chr12-25250908-CGCCGCCGCG-C
• rs397517035
• NM_033360.4:c.-178_-170delCGCGGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr12-25250908-CGCCGCCGCG-C
• chr12-25250908-CGCCGCCGCG-CGCCGCCGCGGCCGCCGCG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004985.5(KRAS):​c.-178_-170delCGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000797 in 251,066 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000071 (0 hom.)
• Consequence: KRAS NM_004985.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.72
• Publications: 0 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: PanelApp Australia, Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• Noonan syndrome

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

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

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet
• 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

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-25250908-CGCCGCCGCG-C is Benign according to our data. Variant chr12-25250908-CGCCGCCGCG-C is described in ClinVar as Benign. ClinVar VariationId is 45112.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000855 (13/152032) while in subpopulation NFE AF = 0.000191 (13/67962). AF 95% confidence interval is 0.000112. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 13 AD gene.

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.-178_-170delCGCGGCGGC		5_prime_UTR	Exon 1 of 6	NP_203524.1	P01116-1
	KRAS	NM_004985.5	MANE Select	c.-178_-170delCGCGGCGGC		5_prime_UTR	Exon 1 of 5	NP_004976.2
	KRAS	NM_001369786.1		c.-165_-157delCGCGGCGGC		5_prime_UTR	Exon 1 of 6	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.-178_-170delCGCGGCGGC		5_prime_UTR	Exon 1 of 6	ENSP00000256078.5	P01116-1
	KRAS	ENST00000311936.8	TSL:1 MANE Select	c.-178_-170delCGCGGCGGC		5_prime_UTR	Exon 1 of 5	ENSP00000308495.3	P01116-2
	KRAS	ENST00000556131.2	TSL:1	c.-178_-170delCGCGGCGGC		5_prime_UTR	Exon 1 of 3	ENSP00000451856.1	G3V4K2

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152032 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000707 AC: 7 AN: 99034 Hom.: 0 AF XY: 0.0000941 AC XY: 5 AN XY: 53114

African (AFR) AF: 0.00 AC: 0 AN: 3272

American (AMR) AF: 0.00 AC: 0 AN: 2164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4334

East Asian (EAS) AF: 0.00 AC: 0 AN: 10814

South Asian (SAS) AF: 0.00 AC: 0 AN: 4082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 534

European-Non Finnish (NFE) AF: 0.0000764 AC: 5 AN: 65454

Other (OTH) AF: 0.000290 AC: 2 AN: 6904

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152032 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74270

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000151

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs397517035; hg19: chr12-25403842;