NM_004985.5:c.*4066dupA

Variant names:

• chr12-25205728-C-CT
• rs34719539
• NM_033360.4:c.*4187dupA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004985.5(KRAS):​c.*4066dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: KRAS NM_004985.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• 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]

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: Uncertain_significance. The variant received 0 ACMG points.

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.*4187dupA		3_prime_UTR	Exon 6 of 6	NP_203524.1	P01116-1
	KRAS	NM_004985.5	MANE Select	c.*4066dupA		3_prime_UTR	Exon 5 of 5	NP_004976.2
	KRAS	NM_001369786.1		c.*4187dupA		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.*4187dupA		3_prime_UTR	Exon 6 of 6	ENSP00000256078.5	P01116-1
	KRAS	ENST00000311936.8	TSL:1 MANE Select	c.*4066dupA		3_prime_UTR	Exon 5 of 5	ENSP00000308495.3	P01116-2
	KRAS	ENST00000685328.1		c.*4066dupA		3_prime_UTR	Exon 5 of 5	ENSP00000508921.1	P01116-2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000145 AC: 1 AN: 68910 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 31892

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3374

American (AMR) AF: 0.00 AC: 0 AN: 2076

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 9748

South Asian (SAS) AF: 0.00 AC: 0 AN: 596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 60

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 432

European-Non Finnish (NFE) AF: 0.0000235 AC: 1 AN: 42528

Other (OTH) AF: 0.00 AC: 0 AN: 5762

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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;