12-25206009-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004985.5(KRAS):c.*3786A>G 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 209,594 control chromosomes in the GnomAD database, including 28,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (19382 hom., cov: 31)
  • Exomes 𝑓: 0.56 (9548 hom.)
• Consequence: KRAS NM_004985.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.682

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-25206009-T-C is Benign according to our data. Variant chr12-25206009-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 308065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_004985.5	c.*3786A>G		3_prime_UTR_variant	5/5	ENST00000311936.8
KRAS	NM_033360.4	c.*3907A>G		3_prime_UTR_variant	6/6	ENST00000256078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRAS	ENST00000256078.10	c.*3907A>G		3_prime_UTR_variant	6/6	1	NM_033360.4	A1
KRAS	ENST00000311936.8	c.*3786A>G		3_prime_UTR_variant	5/5	1	NM_004985.5	P4

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74797 AN: 151598 Hom.: 19371 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.506

GnomAD4 exome AF: 0.564 AC: 32621 AN: 57880 Hom.: 9548 Cov.: 0 AF XY: 0.567 AC XY: 15203 AN XY: 26818

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.492

Gnomad4 ASJ exome AF: 0.636

Gnomad4 EAS exome AF: 0.782

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.529

Gnomad4 OTH exome AF: 0.538

GnomAD4 genome AF: 0.493 AC: 74837 AN: 151714 Hom.: 19382 Cov.: 31 AF XY: 0.499 AC XY: 36985 AN XY: 74118

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.507

Alfa AF: 0.524 Hom.: 4426

Bravo AF: 0.482

Asia WGS AF: 0.690 AC: 2388 AN: 3464

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Noonan syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	7.4
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8720; hg19: chr12-25358943;