rs7960917

Variant names:

• chr12-25208712-T-C
• rs7960917
• NM_033360.4:c.*1204A>G

Variant summary

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

The NM_033360.4(KRAS):​c.*1204A>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 0.187 in 232,690 control chromosomes in the GnomAD database, including 4,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2717 hom., cov: 32)
  • Exomes 𝑓: 0.19 (1509 hom.)
• Consequence: KRAS NM_033360.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00200
• Publications: 16 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=-0.86).
• BP6: Variant 12-25208712-T-C is Benign according to our data. Variant chr12-25208712-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 308110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033360.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRAS	NM_033360.4	MANE Plus Clinical	c.*1204A>G		3_prime_UTR	Exon 6 of 6	NP_203524.1
	KRAS	NM_004985.5	MANE Select	c.*1083A>G		3_prime_UTR	Exon 5 of 5	NP_004976.2
	KRAS	NM_001369786.1		c.*1204A>G		3_prime_UTR	Exon 6 of 6	NP_001356715.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRAS	ENST00000256078.10	TSL:1 MANE Plus Clinical	c.*1204A>G		3_prime_UTR	Exon 6 of 6	ENSP00000256078.5
	KRAS	ENST00000311936.8	TSL:1 MANE Select	c.*1083A>G		3_prime_UTR	Exon 5 of 5	ENSP00000308495.3
	KRAS	ENST00000686877.1		n.*1621A>G		non_coding_transcript_exon	Exon 6 of 6	ENSP00000510431.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27886 AN: 152082 Hom.: 2711 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0980

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.193 AC: 15519 AN: 80490 Hom.: 1509 Cov.: 0 AF XY: 0.191 AC XY: 7088 AN XY: 37050

African (AFR) AF: 0.137 AC: 528 AN: 3860

American (AMR) AF: 0.189 AC: 468 AN: 2480

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 789 AN: 5082

East Asian (EAS) AF: 0.128 AC: 1444 AN: 11282

South Asian (SAS) AF: 0.191 AC: 133 AN: 698

European-Finnish (FIN) AF: 0.197 AC: 24 AN: 122

Middle Eastern (MID) AF: 0.214 AC: 105 AN: 490

European-Non Finnish (NFE) AF: 0.217 AC: 10804 AN: 49782

Other (OTH) AF: 0.183 AC: 1224 AN: 6694

GnomAD4 genome AF: 0.183 AC: 27905 AN: 152200 Hom.: 2717 Cov.: 32 AF XY: 0.179 AC XY: 13320 AN XY: 74410

African (AFR) AF: 0.134 AC: 5565 AN: 41508

American (AMR) AF: 0.192 AC: 2936 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3470

East Asian (EAS) AF: 0.0981 AC: 509 AN: 5190

South Asian (SAS) AF: 0.193 AC: 931 AN: 4824

European-Finnish (FIN) AF: 0.150 AC: 1586 AN: 10592

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14939 AN: 68018

Other (OTH) AF: 0.198 AC: 419 AN: 2112

Alfa AF: 0.203 Hom.: 855

Bravo AF: 0.181

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.59
PhyloP100		0.0020
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: rs7960917; hg19: chr12-25361646;