12-25205728-CTT-C

Position:

• chr12-25205728-CTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004985.5(KRAS):​c.*4065_*4066del 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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_004985.5	c.*4065_*4066del		3_prime_UTR_variant	5/5	ENST00000311936.8
KRAS	NM_033360.4	c.*4186_*4187del		3_prime_UTR_variant	6/6	ENST00000256078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRAS	ENST00000256078.10	c.*4186_*4187del		3_prime_UTR_variant	6/6	1	NM_033360.4	A1
KRAS	ENST00000311936.8	c.*4065_*4066del		3_prime_UTR_variant	5/5	1	NM_004985.5	P4

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

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.490

Gnomad4 ASJ exome AF: 0.637

Gnomad4 EAS exome AF: 0.789

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.533

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.542

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

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.505

Bravo AF: 0.478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Cardio-facio-cutaneous syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Noonan syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34719539; hg19: chr12-25358662;