rs61764374

Positions:

• chr12-25205484-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BA1

The NM_004985.5(KRAS):​c.*4311A>G variant causes a 3 prime UTR change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 215,318 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (126 hom., cov: 32)
  • Exomes 𝑓: 0.042 (64 hom.)
• Consequence: KRAS NM_004985.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.35

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BP6: Variant 12-25205484-T-C is Benign according to our data. Variant chr12-25205484-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 308057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_004985.5	c.*4311A>G		3_prime_UTR_variant	5/5	ENST00000311936.8
KRAS	NM_033360.4	c.*4432A>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.*4432A>G		3_prime_UTR_variant	6/6	1	NM_033360.4	A1
KRAS	ENST00000311936.8	c.*4311A>G		3_prime_UTR_variant	5/5	1	NM_004985.5	P4

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5643 AN: 151002 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.00981

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0585

Gnomad OTH AF: 0.0447

GnomAD4 exome AF: 0.0421 AC: 2705 AN: 64194 Hom.: 64 Cov.: 0 AF XY: 0.0437 AC XY: 1297 AN XY: 29664

Gnomad4 AFR exome AF: 0.00637

Gnomad4 AMR exome AF: 0.0252

Gnomad4 ASJ exome AF: 0.0551

Gnomad4 EAS exome AF: 0.000108

Gnomad4 SAS exome AF: 0.0258

Gnomad4 FIN exome AF: 0.0445

Gnomad4 NFE exome AF: 0.0542

Gnomad4 OTH exome AF: 0.0423

GnomAD4 genome AF: 0.0373 AC: 5640 AN: 151124 Hom.: 126 Cov.: 32 AF XY: 0.0351 AC XY: 2597 AN XY: 73888

Gnomad4 AFR AF: 0.00978

Gnomad4 AMR AF: 0.0298

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0400

Gnomad4 NFE AF: 0.0585

Gnomad4 OTH AF: 0.0433

Alfa AF: 0.0518 Hom.: 41

Bravo AF: 0.0339

Asia WGS AF: 0.0140 AC: 47 AN: 3478

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	-0.18
CADD	Benign	17
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61764374; hg19: chr12-25358418;