rs712

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-25209618-A-C
• chr12-25209618-A-G
• chr12-25209618-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.*177T>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 0.536 in 1,341,780 control chromosomes in the GnomAD database, including 198,236 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 (18345 hom., cov: 31)
  • Exomes 𝑓: 0.54 (179891 hom.)
• Consequence: KRAS NM_004985.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 12-25209618-A-C is Benign according to our data. Variant chr12-25209618-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 40467.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.

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.*298T>G		3_prime_UTR	Exon 6 of 6	NP_203524.1	P01116-1
	KRAS	NM_004985.5	MANE Select	c.*177T>G		3_prime_UTR	Exon 5 of 5	NP_004976.2
	KRAS	NM_001369786.1		c.*298T>G		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.*298T>G		3_prime_UTR	Exon 6 of 6	ENSP00000256078.5	P01116-1
	KRAS	ENST00000311936.8	TSL:1 MANE Select	c.*177T>G		3_prime_UTR	Exon 5 of 5	ENSP00000308495.3	P01116-2
	KRAS	ENST00000685328.1		c.*177T>G		3_prime_UTR	Exon 5 of 5	ENSP00000508921.1	P01116-2

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71110 AN: 151780 Hom.: 18340 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.544 AC: 647866 AN: 1189882 Hom.: 179891 Cov.: 30 AF XY: 0.547 AC XY: 313066 AN XY: 572148

African (AFR) AF: 0.226 AC: 5597 AN: 24794

American (AMR) AF: 0.504 AC: 6171 AN: 12240

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 10739 AN: 16804

East Asian (EAS) AF: 0.796 AC: 23351 AN: 29322

South Asian (SAS) AF: 0.656 AC: 29540 AN: 44998

European-Finnish (FIN) AF: 0.558 AC: 16892 AN: 30290

Middle Eastern (MID) AF: 0.558 AC: 1817 AN: 3254

European-Non Finnish (NFE) AF: 0.538 AC: 526886 AN: 979646

Other (OTH) AF: 0.554 AC: 26873 AN: 48534

GnomAD4 genome AF: 0.468 AC: 71139 AN: 151898 Hom.: 18345 Cov.: 31 AF XY: 0.474 AC XY: 35183 AN XY: 74202

African (AFR) AF: 0.244 AC: 10100 AN: 41464

American (AMR) AF: 0.492 AC: 7507 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2166 AN: 3468

East Asian (EAS) AF: 0.800 AC: 4144 AN: 5178

South Asian (SAS) AF: 0.668 AC: 3208 AN: 4802

European-Finnish (FIN) AF: 0.542 AC: 5690 AN: 10500

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

European-Non Finnish (NFE) AF: 0.541 AC: 36777 AN: 67920

Other (OTH) AF: 0.486 AC: 1027 AN: 2112

Alfa AF: 0.495 Hom.: 2786

Bravo AF: 0.455

Asia WGS AF: 0.681 AC: 2365 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Noonan syndrome (1)
-	-	1	Noonan syndrome and Noonan-related syndrome (1)
-	-	1	RASopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=99/1	polymorphism (auto)

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; COSMIC: COSV55614059;