19-51354404-C-T

Position:

chr19-51354404-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000354232.8(ETFB):c.235G>A(p.Val79Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,613,986 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 23 hom. )

Consequence

ETFB
ENST00000354232.8 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.184

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005254954).

BP6

Variant 19-51354404-C-T is Benign according to our data. Variant chr19-51354404-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 137229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00359 (547/152310) while in subpopulation NFE AF= 0.00494 (336/68018). AF 95% confidence interval is 0.0045. There are 4 homozygotes in gnomad4. There are 273 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ETFB	NM_001985.3 linkuse as main transcript	c.58-96G>A		intron_variant		ENST00000309244.9	NP_001976.1
ETFB	NM_001014763.1 linkuse as main transcript	c.235G>A	p.Val79Ile	missense_variant	1/5		NP_001014763.1
ETFB	XM_024451418.2 linkuse as main transcript	c.-54-96G>A		intron_variant			XP_024307186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETFB	ENST00000354232.8 linkuse as main transcript	c.235G>A	p.Val79Ile	missense_variant	1/5	1		ENSP00000346173		P38117-2
ETFB	ENST00000309244.9 linkuse as main transcript	c.58-96G>A		intron_variant		1	NM_001985.3	ENSP00000311930	P1	P38117-1
ETFB	ENST00000596253.1 linkuse as main transcript	c.58-96G>A		intron_variant		3		ENSP00000469628
ETFB	ENST00000593992.1 linkuse as main transcript	n.81-96G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00359

AC:

547

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00894

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00494

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00451

AC:

1125

AN:

249426

Hom.:

AF XY:

0.00453

AC XY:

611

AN XY:

134984

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.00284

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.00646

Gnomad OTH exome

AF:

0.00556

GnomAD4 exome

AF:

0.00477

AC:

6978

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

3349

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00320

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00137

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.00528

Gnomad4 OTH exome

AF:

0.00439

GnomAD4 genome

AF:

0.00359

AC:

547

AN:

152310

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

273

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00894

Gnomad4 NFE

AF:

0.00494

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00510

Hom.:

Bravo

AF:

0.00337

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00511

AC:

621

EpiCase

AF:

0.00463

EpiControl

AF:

0.00475

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 19, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	ETFB: BP4, BS2 -

Multiple acyl-CoA dehydrogenase deficiency

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 08, 2022	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 25, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

ETFB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 24, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

2.8

DANN

Uncertain

0.98

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0053

MetaSVM

Benign

-0.84

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

0.020

REVEL

Benign

0.032

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.18

Vest4

0.059

MVP

0.86

MPC

0.18

ClinPred

0.020

GERP RS

1.7

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over