chr12-25206907-T-C

Variant names:

• chr12-25206907-T-C
• rs13096
• NM_004985.5:c.*2888A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004985.5(KRAS):​c.*2888A>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 0.498 in 201,246 control chromosomes in the GnomAD database, including 27,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (18538 hom., cov: 32)
  • Exomes 𝑓: 0.57 (8470 hom.)
• Consequence: KRAS NM_004985.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0860
• Publications: 27 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 12-25206907-T-C is Benign according to our data. Variant chr12-25206907-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 308082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
KRAS	NM_004985.5	c.*2888A>G		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	ENST00000311936.8	c.*2888A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_004985.5	ENSP00000308495.3

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71832 AN: 151930 Hom.: 18531 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.487

GnomAD4 exome AF: 0.574 AC: 28261 AN: 49198 Hom.: 8470 Cov.: 0 AF XY: 0.577 AC XY: 13199 AN XY: 22860

African (AFR) AF: 0.261 AC: 564 AN: 2164

American (AMR) AF: 0.498 AC: 662 AN: 1328

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 1975 AN: 3132

East Asian (EAS) AF: 0.791 AC: 6172 AN: 7806

South Asian (SAS) AF: 0.690 AC: 294 AN: 426

European-Finnish (FIN) AF: 0.462 AC: 12 AN: 26

Middle Eastern (MID) AF: 0.576 AC: 175 AN: 304

European-Non Finnish (NFE) AF: 0.541 AC: 16209 AN: 29952

Other (OTH) AF: 0.541 AC: 2198 AN: 4060

GnomAD4 genome AF: 0.473 AC: 71865 AN: 152048 Hom.: 18538 Cov.: 32 AF XY: 0.479 AC XY: 35579 AN XY: 74320

African (AFR) AF: 0.258 AC: 10710 AN: 41478

American (AMR) AF: 0.494 AC: 7542 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2163 AN: 3468

East Asian (EAS) AF: 0.801 AC: 4147 AN: 5180

South Asian (SAS) AF: 0.667 AC: 3220 AN: 4824

European-Finnish (FIN) AF: 0.544 AC: 5745 AN: 10562

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36786 AN: 67952

Other (OTH) AF: 0.488 AC: 1031 AN: 2114

Alfa AF: 0.519 Hom.: 17891

Bravo AF: 0.459

Asia WGS AF: 0.688 AC: 2391 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Noonan syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.98
DANN	Benign	0.54
PhyloP100		-0.086
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13096; hg19: chr12-25359841; COSMIC: COSV105058559; COSMIC: COSV105058559;