rs61764370

Variant names:

• chr12-25207290-A-C
• rs61764370
• NM_033360.4:c.*2626T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-25207290-A-C
• chr12-25207290-A-G
• chr12-25207290-A-T

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.*2505T>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 0.0642 in 195,932 control chromosomes in the GnomAD database, including 528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (390 hom., cov: 31)
  • Exomes 𝑓: 0.073 (138 hom.)
• Consequence: KRAS NM_004985.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.836
• Publications: 135 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=-0.87).
• BP6: Variant 12-25207290-A-C is Benign according to our data. Variant chr12-25207290-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 308084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0913 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.*2626T>G		3_prime_UTR	Exon 6 of 6	NP_203524.1	P01116-1
	KRAS	NM_004985.5	MANE Select	c.*2505T>G		3_prime_UTR	Exon 5 of 5	NP_004976.2
	KRAS	NM_001369786.1		c.*2626T>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.*2626T>G		3_prime_UTR	Exon 6 of 6	ENSP00000256078.5	P01116-1
	KRAS	ENST00000311936.8	TSL:1 MANE Select	c.*2505T>G		3_prime_UTR	Exon 5 of 5	ENSP00000308495.3	P01116-2
	KRAS	ENST00000685328.1		c.*2505T>G		3_prime_UTR	Exon 5 of 5	ENSP00000508921.1	P01116-2

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9391 AN: 152092 Hom.: 389 Cov.: 31

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.0923

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0932

Gnomad OTH AF: 0.0773

GnomAD4 exome AF: 0.0726 AC: 3176 AN: 43722 Hom.: 138 Cov.: 0 AF XY: 0.0744 AC XY: 1516 AN XY: 20390

African (AFR) AF: 0.0251 AC: 45 AN: 1792

American (AMR) AF: 0.0706 AC: 85 AN: 1204

Ashkenazi Jewish (ASJ) AF: 0.0966 AC: 272 AN: 2816

East Asian (EAS) AF: 0.000137 AC: 1 AN: 7304

South Asian (SAS) AF: 0.00847 AC: 3 AN: 354

European-Finnish (FIN) AF: 0.0833 AC: 2 AN: 24

Middle Eastern (MID) AF: 0.0660 AC: 19 AN: 288

European-Non Finnish (NFE) AF: 0.0936 AC: 2459 AN: 26276

Other (OTH) AF: 0.0791 AC: 290 AN: 3664

GnomAD4 genome AF: 0.0617 AC: 9396 AN: 152210 Hom.: 390 Cov.: 31 AF XY: 0.0588 AC XY: 4375 AN XY: 74424

African (AFR) AF: 0.0190 AC: 789 AN: 41542

American (AMR) AF: 0.0789 AC: 1206 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0923 AC: 320 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4820

European-Finnish (FIN) AF: 0.0348 AC: 369 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0932 AC: 6340 AN: 68004

Other (OTH) AF: 0.0764 AC: 161 AN: 2106

Alfa AF: 0.0660 Hom.: 138

Bravo AF: 0.0638

Asia WGS AF: 0.0120 AC: 41 AN: 3478

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)
-	-	1	RASopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.73
PhyloP100		0.84
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: rs61764370; hg19: chr12-25360224;