rs11047892

Variant names:

• chr12-25205099-T-A
• rs11047892
• NM_001001660.3:c.*787T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-25205099-T-A
• chr12-25205099-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001660.3(ETFRF1):​c.*787T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 215,708 control chromosomes in the GnomAD database, including 1,542 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (1135 hom., cov: 33)
  • Exomes 𝑓: 0.097 (407 hom.)
• Consequence: ETFRF1 NM_001001660.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 8 publications found

Genes affected

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]

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]

KRAS Gene-Disease associations (from GenCC):

• cardiofaciocutaneous syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Noonan syndrome 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
• cardiofaciocutaneous syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen
• linear nevus sebaceous syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Costello syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome with multiple lentigines

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome-like disorder with loose anagen hair

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001660.3. 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
	ETFRF1	NM_001001660.3	MANE Select	c.*787T>A		3_prime_UTR	Exon 3 of 3	NP_001001660.2	Q6IPR1
	KRAS	NM_033360.4	MANE Plus Clinical	c.*4817A>T		downstream_gene	N/A	NP_203524.1	P01116-1
	KRAS	NM_004985.5	MANE Select	c.*4696A>T		downstream_gene	N/A	NP_004976.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETFRF1	ENST00000381356.9	TSL:1 MANE Select	c.*787T>A		3_prime_UTR	Exon 3 of 3	ENSP00000370761.4	Q6IPR1
	ETFRF1	ENST00000557540.7	TSL:2	c.*787T>A		3_prime_UTR	Exon 3 of 3	ENSP00000450584.2	Q6IPR1
	ETFRF1	ENST00000878628.1		c.*787T>A		3_prime_UTR	Exon 3 of 3	ENSP00000548687.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15311 AN: 152026 Hom.: 1135 Cov.: 33

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0767

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0970

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.0837

GnomAD4 exome AF: 0.0971 AC: 6171 AN: 63564 Hom.: 407 Cov.: 0 AF XY: 0.0972 AC XY: 2867 AN XY: 29502

African (AFR) AF: 0.0229 AC: 67 AN: 2924

American (AMR) AF: 0.0690 AC: 132 AN: 1912

Ashkenazi Jewish (ASJ) AF: 0.0587 AC: 237 AN: 4040

East Asian (EAS) AF: 0.000322 AC: 3 AN: 9318

South Asian (SAS) AF: 0.110 AC: 62 AN: 564

European-Finnish (FIN) AF: 0.272 AC: 112 AN: 412

Middle Eastern (MID) AF: 0.0483 AC: 20 AN: 414

European-Non Finnish (NFE) AF: 0.130 AC: 5023 AN: 38666

Other (OTH) AF: 0.0969 AC: 515 AN: 5314

GnomAD4 genome AF: 0.101 AC: 15305 AN: 152144 Hom.: 1135 Cov.: 33 AF XY: 0.105 AC XY: 7835 AN XY: 74346

African (AFR) AF: 0.0223 AC: 927 AN: 41556

American (AMR) AF: 0.0766 AC: 1170 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5186

South Asian (SAS) AF: 0.0969 AC: 467 AN: 4820

European-Finnish (FIN) AF: 0.272 AC: 2873 AN: 10570

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9371 AN: 67940

Other (OTH) AF: 0.0828 AC: 175 AN: 2114

Alfa AF: 0.0696 Hom.: 114

Bravo AF: 0.0832

Asia WGS AF: 0.0390 AC: 137 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.69
PhyloP100		-0.0030
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: rs11047892; hg19: chr12-25358033;