chr12-25209618-A-T

Variant names:

• chr12-25209618-A-T
• rs712
• NM_033360.4:c.*298T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033360.4(KRAS):​c.*298T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,191,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: KRAS NM_033360.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• Publications: 93 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRAS	NM_033360.4	c.*298T>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000256078.10	NP_203524.1
KRAS	NM_004985.5	c.*177T>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000311936.8	NP_004976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000256078.10	c.*298T>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_033360.4	ENSP00000256078.5
KRAS	ENST00000311936.8	c.*177T>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_004985.5	ENSP00000308495.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000252 AC: 3 AN: 1191170 Hom.: 0 Cov.: 30 AF XY: 0.00000349 AC XY: 2 AN XY: 572758

African (AFR) AF: 0.00 AC: 0 AN: 24812

American (AMR) AF: 0.00 AC: 0 AN: 12272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16828

East Asian (EAS) AF: 0.00 AC: 0 AN: 29346

South Asian (SAS) AF: 0.0000222 AC: 1 AN: 45080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3256

European-Non Finnish (NFE) AF: 0.00000204 AC: 2 AN: 980602

Other (OTH) AF: 0.00 AC: 0 AN: 48586

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs712; hg19: chr12-25362552;