chr12-25206111-G-GA

Position:

• chr12-25206111-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004985.5(KRAS):​c.*3683_*3684insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 205,816 control chromosomes in the GnomAD database, including 1,689 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.086 (1654 hom., cov: 31)
  • Exomes 𝑓: 0.025 (35 hom.)
• Consequence: KRAS NM_004985.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.614

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-25206111-G-GA is Benign according to our data. Variant chr12-25206111-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 308068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_004985.5	c.*3683_*3684insT		3_prime_UTR_variant	5/5	ENST00000311936.8
KRAS	NM_033360.4	c.*3804_*3805insT		3_prime_UTR_variant	6/6	ENST00000256078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRAS	ENST00000256078.10	c.*3804_*3805insT		3_prime_UTR_variant	6/6	1	NM_033360.4	A1
KRAS	ENST00000311936.8	c.*3683_*3684insT		3_prime_UTR_variant	5/5	1	NM_004985.5	P4

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 12756 AN: 148654 Hom.: 1652 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.0238

Gnomad EAS AF: 0.00234

Gnomad SAS AF: 0.00212

Gnomad FIN AF: 0.000205

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.00498

Gnomad OTH AF: 0.0646

GnomAD4 exome AF: 0.0248 AC: 1413 AN: 57056 Hom.: 35 Cov.: 0 AF XY: 0.0239 AC XY: 630 AN XY: 26408

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.0311

Gnomad4 ASJ exome AF: 0.0277

Gnomad4 EAS exome AF: 0.00417

Gnomad4 SAS exome AF: 0.00816

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.0363

GnomAD4 genome AF: 0.0859 AC: 12775 AN: 148760 Hom.: 1654 Cov.: 31 AF XY: 0.0833 AC XY: 6036 AN XY: 72456

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.0314

Gnomad4 ASJ AF: 0.0238

Gnomad4 EAS AF: 0.00235

Gnomad4 SAS AF: 0.00191

Gnomad4 FIN AF: 0.000205

Gnomad4 NFE AF: 0.00499

Gnomad4 OTH AF: 0.0641

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Cardio-facio-cutaneous syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Noonan syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs142323886; hg19: chr12-25359045;