Genetic Variant NM_001001660.3:c.-38+401A>C (chr12-25195738-A-C) – 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.-38+401A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,430 control chromosomes in the GnomAD database, including 16,980 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 0.44 ( 16953 hom., cov: 32)

Exomes 𝑓: 0.39 ( 27 hom. )

Consequence

ETFRF1
NM_001001660.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0700

Publications

20 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:

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 (EAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ETFRF1	NM_001001660.3 link	c.-38+401A>C	intron_variant	Intron 1 of 2	ENST00000381356.9	NP_001001660.2	Q6IPR1
ETFRF1	XM_017018850.3 link	c.-8132A>C	5_prime_UTR_variant	Exon 1 of 3		XP_016874339.1	Q6IPR1
ETFRF1	XM_005253319.5 link	c.-38+397A>C	intron_variant	Intron 1 of 2		XP_005253376.1	Q6IPR1
ETFRF1	XM_005253320.5 link	c.-146+401A>C	intron_variant	Intron 1 of 3		XP_005253377.1	Q6IPR1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETFRF1	ENST00000381356.9 link	c.-38+401A>C		intron_variant	Intron 1 of 2	1	NM_001001660.3	ENSP00000370761.4		Q6IPR1

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67584

AN:

151982

Hom.:

16952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.796

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.528

Gnomad OTH

AF:

0.461

GnomAD4 exome

AF:

0.394

AC:

130

AN:

330

Hom.:

Cov.:

AF XY:

0.446

AC XY:

AN XY:

204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.150

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.408

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.411

AC:

AN:

202

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.444

AC:

67604

AN:

152100

Hom.:

16953

Cov.:

AF XY:

0.449

AC XY:

33374

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.201

AC:

8325

AN:

41504

American (AMR)

AF:

0.481

AC:

7349

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1957

AN:

3470

East Asian (EAS)

AF:

0.796

AC:

4122

AN:

5180

South Asian (SAS)

AF:

0.576

AC:

2778

AN:

4820

European-Finnish (FIN)

AF:

0.539

AC:

5683

AN:

10544

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.528

AC:

35899

AN:

67978

Other (OTH)

AF:

0.463

AC:

978

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1770

3540

5309

7079

8849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.499

Hom.:

31928

Bravo

AF:

0.430

Asia WGS

AF:

0.652

AC:

2266

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.1

(source)

DANN

Benign

0.68

PhyloP100

-0.070

PromoterAI

-0.022

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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