dbSNP rs11047892: ETFRF1:c.*787T>A (chr12-25205099-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

Publications

8 publications found

Variant links:

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]

ETFRF1 links:

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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics, PanelApp Australia
Noonan syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Noonan syndrome 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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

KRAS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETFRF1	NM_001001660.3 link	c.*787T>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000381356.9	NP_001001660.2	Q6IPR1
KRAS	NM_004985.5 link	c.*4696A>T		downstream_gene_variant		ENST00000311936.8	NP_004976.2	P01116-2A0A024RAV5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETFRF1	ENST00000381356.9 link	c.*787T>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_001001660.3	ENSP00000370761.4		Q6IPR1
KRAS	ENST00000311936.8 link	c.*4696A>T		downstream_gene_variant		1	NM_004985.5	ENSP00000308495.3		P01116-2

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15311

AN:

152026

Hom.:

1135

Cov.:

show subpopulations

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.:

AF XY:

0.0972

AC XY:

2867

AN XY:

29502

show subpopulations

African (AFR)

AF:

0.0229

AC:

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:

AN:

9318

South Asian (SAS)

AF:

0.110

AC:

AN:

564

European-Finnish (FIN)

AF:

0.272

AC:

112

AN:

412

Middle Eastern (MID)

AF:

0.0483

AC:

AN:

414

European-Non Finnish (NFE)

AF:

0.130

AC:

5023

AN:

38666

Other (OTH)

AF:

0.0969

AC:

515

AN:

5314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

268

535

803

1070

1338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.101

AC:

15305

AN:

152144

Hom.:

1135

Cov.:

AF XY:

0.105

AC XY:

7835

AN XY:

74346

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9371

AN:

67940

Other (OTH)

AF:

0.0828

AC:

175

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

684

1368

2051

2735

3419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.9

(source)

DANN

Benign

0.69

PhyloP100

-0.0030

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over