rs9266

Variant names:

• chr12-25209283-A-G
• rs9266
• NM_033360.4:c.*633T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-25209283-A-G
• chr12-25209283-A-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_004985.5(KRAS):​c.*512T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 644,948 control chromosomes in the GnomAD database, including 100,913 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 (19406 hom., cov: 31)
  • Exomes 𝑓: 0.57 (81507 hom.)
• Consequence: KRAS NM_004985.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.472
• Publications: 48 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 12-25209283-A-G is Benign according to our data. Variant chr12-25209283-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 308118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

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.*633T>C		3_prime_UTR	Exon 6 of 6	NP_203524.1	P01116-1
	KRAS	NM_004985.5	MANE Select	c.*512T>C		3_prime_UTR	Exon 5 of 5	NP_004976.2
	KRAS	NM_001369786.1		c.*633T>C		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.*633T>C		3_prime_UTR	Exon 6 of 6	ENSP00000256078.5	P01116-1
	KRAS	ENST00000311936.8	TSL:1 MANE Select	c.*512T>C		3_prime_UTR	Exon 5 of 5	ENSP00000308495.3	P01116-2
	KRAS	ENST00000685328.1		c.*512T>C		3_prime_UTR	Exon 5 of 5	ENSP00000508921.1	P01116-2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74841 AN: 151788 Hom.: 19394 Cov.: 31

Gnomad AFR AF: 0.328

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: 0.543

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.506

GnomAD2 exomes AF: 0.581 AC: 61555 AN: 106036 AF XY: 0.584

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.546

Gnomad ASJ exome AF: 0.632

Gnomad EAS exome AF: 0.806

Gnomad FIN exome AF: 0.560

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.567 AC: 279771 AN: 493042 Hom.: 81507 Cov.: 4 AF XY: 0.572 AC XY: 152847 AN XY: 267114

African (AFR) AF: 0.328 AC: 4430 AN: 13524

American (AMR) AF: 0.530 AC: 15036 AN: 28350

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 11648 AN: 18242

East Asian (EAS) AF: 0.797 AC: 24143 AN: 30292

South Asian (SAS) AF: 0.655 AC: 31866 AN: 48682

European-Finnish (FIN) AF: 0.563 AC: 17492 AN: 31044

Middle Eastern (MID) AF: 0.556 AC: 2097 AN: 3774

European-Non Finnish (NFE) AF: 0.541 AC: 157566 AN: 291188

Other (OTH) AF: 0.554 AC: 15493 AN: 27946

GnomAD4 genome AF: 0.493 AC: 74883 AN: 151906 Hom.: 19406 Cov.: 31 AF XY: 0.499 AC XY: 37018 AN XY: 74242

African (AFR) AF: 0.328 AC: 13600 AN: 41422

American (AMR) AF: 0.501 AC: 7648 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2165 AN: 3468

East Asian (EAS) AF: 0.801 AC: 4139 AN: 5168

South Asian (SAS) AF: 0.668 AC: 3217 AN: 4818

European-Finnish (FIN) AF: 0.543 AC: 5715 AN: 10532

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

European-Non Finnish (NFE) AF: 0.542 AC: 36812 AN: 67932

Other (OTH) AF: 0.507 AC: 1067 AN: 2104

Alfa AF: 0.532 Hom.: 94855

Bravo AF: 0.482

Asia WGS AF: 0.691 AC: 2401 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Noonan syndrome (1)
-	-	1	Noonan syndrome and Noonan-related syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		0.47
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9266; hg19: chr12-25362217;