chr12-25205728-CTT-C

Variant names:

• chr12-25205728-CTT-C
• rs34719539
• NM_033360.4:c.*4186_*4187delAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004985.5(KRAS):​c.*4065_*4066delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 220,254 control chromosomes in the GnomAD database, including 30,657 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (19088 hom., cov: 0)
  • Exomes 𝑓: 0.57 (11569 hom.)
• Consequence: KRAS NM_004985.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.12
• Publications: 1 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]

ETFRF1 (HGNC:27052): (electron transfer flavoprotein regulatory factor 1) Involved in respiratory electron transport chain. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP6: Variant 12-25205728-CTT-C is Benign according to our data. Variant chr12-25205728-CTT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 308062.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 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.*4186_*4187delAA		3_prime_UTR	Exon 6 of 6	NP_203524.1	P01116-1
	KRAS	NM_004985.5	MANE Select	c.*4065_*4066delAA		3_prime_UTR	Exon 5 of 5	NP_004976.2
	KRAS	NM_001369786.1		c.*4186_*4187delAA		3_prime_UTR	Exon 6 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.*4186_*4187delAA		3_prime_UTR	Exon 6 of 6	ENSP00000256078.5	P01116-1
	KRAS	ENST00000311936.8	TSL:1 MANE Select	c.*4065_*4066delAA		3_prime_UTR	Exon 5 of 5	ENSP00000308495.3	P01116-2
	KRAS	ENST00000685328.1		c.*4065_*4066delAA		3_prime_UTR	Exon 5 of 5	ENSP00000508921.1	P01116-2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 73976 AN: 151528 Hom.: 19078 Cov.: 0

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.568 AC: 38937 AN: 68608 Hom.: 11569 AF XY: 0.570 AC XY: 18115 AN XY: 31762

African (AFR) AF: 0.317 AC: 1069 AN: 3368

American (AMR) AF: 0.490 AC: 1014 AN: 2070

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2747 AN: 4312

East Asian (EAS) AF: 0.789 AC: 7672 AN: 9720

South Asian (SAS) AF: 0.663 AC: 394 AN: 594

European-Finnish (FIN) AF: 0.533 AC: 32 AN: 60

Middle Eastern (MID) AF: 0.569 AC: 246 AN: 432

European-Non Finnish (NFE) AF: 0.535 AC: 22653 AN: 42318

Other (OTH) AF: 0.542 AC: 3110 AN: 5734

GnomAD4 genome AF: 0.488 AC: 74014 AN: 151646 Hom.: 19088 Cov.: 0 AF XY: 0.494 AC XY: 36571 AN XY: 74084

African (AFR) AF: 0.313 AC: 12946 AN: 41370

American (AMR) AF: 0.499 AC: 7599 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2163 AN: 3468

East Asian (EAS) AF: 0.800 AC: 4125 AN: 5158

South Asian (SAS) AF: 0.667 AC: 3211 AN: 4812

European-Finnish (FIN) AF: 0.543 AC: 5697 AN: 10490

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36692 AN: 67814

Other (OTH) AF: 0.505 AC: 1063 AN: 2104

Alfa AF: 0.377 Hom.: 1051

Bravo AF: 0.478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cardio-facio-cutaneous syndrome (1)
-	-	1	Noonan syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs34719539; hg19: chr12-25358662; COSMIC: COSV55648498; COSMIC: COSV55648498;