Genetic Variant ETFB:c.439-1417C>T (chr19-51348475-G-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_001985.3(ETFB):c.439-1417C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,948 control chromosomes in the GnomAD database, including 16,149 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 0.45 ( 16148 hom., cov: 31)

Exomes 𝑓: 0.38 ( 1 hom. )

Consequence

ETFB
NM_001985.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.121

Publications

2 publications found

Variant links:

Genes affected

ETFB (HGNC:3482): (electron transfer flavoprotein subunit beta) This gene encodes electron-transfer-flavoprotein, beta polypeptide, which shuttles electrons between primary flavoprotein dehydrogenases involved in mitochondrial fatty acid and amino acid catabolism and the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase. The gene deficiencies have been implicated in type II glutaricaciduria. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

ETFB Gene-Disease associations (from GenCC):

multiple acyl-CoA dehydrogenase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ETFB links:

ENSG00000267984 (HGNC:):

ENSG00000267984 links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001985.3. 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
	ETFB	NM_001985.3	MANE Select	c.439-1417C>T		intron	N/A	NP_001976.1	P38117-1
	ETFB	NM_001014763.1		c.712-1417C>T		intron	N/A	NP_001014763.1	P38117-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ETFB	ENST00000309244.9	TSL:1 MANE Select	c.439-1417C>T	intron	N/A	ENSP00000311930.3	P38117-1
ETFB	ENST00000354232.8	TSL:1	c.712-1417C>T	intron	N/A	ENSP00000346173.3	P38117-2
ETFB	ENST00000903309.1		c.514-1417C>T	intron	N/A	ENSP00000573368.1

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69080

AN:

151822

Hom.:

16146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.575

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.439

GnomAD4 exome

AF:

0.375

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.455

AC:

69108

AN:

151940

Hom.:

16148

Cov.:

AF XY:

0.452

AC XY:

33585

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.456

AC:

18892

AN:

41406

American (AMR)

AF:

0.381

AC:

5814

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1141

AN:

3464

East Asian (EAS)

AF:

0.226

AC:

1168

AN:

5168

South Asian (SAS)

AF:

0.233

AC:

1120

AN:

4816

European-Finnish (FIN)

AF:

0.575

AC:

6063

AN:

10546

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33298

AN:

67972

Other (OTH)

AF:

0.434

AC:

914

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1879

3758

5638

7517

9396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.476

Hom.:

2850

Bravo

AF:

0.445

Asia WGS

AF:

0.226

AC:

789

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.4

(source)

DANN

Benign

0.18

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over