rs4886791

Positions:

• chr15-76303909-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000126.4(ETFA):​c.39+7441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,152 control chromosomes in the GnomAD database, including 5,846 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 0.26 (5846 hom., cov: 32)
• Consequence: ETFA NM_000126.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

Genes affected

ETFA (HGNC:3481): (electron transfer flavoprotein subunit alpha) ETFA participates in catalyzing the initial step of the mitochondrial fatty acid beta-oxidation. It shuttles electrons between primary flavoprotein dehydrogenases and the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase. Defects in electron-transfer-flavoprotein have been implicated in type II glutaricaciduria in which multiple acyl-CoA dehydrogenase deficiencies result in large excretion of glutaric, lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ETFA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETFA	NM_000126.4	c.39+7441G>A		intron_variant		ENST00000557943.6	NP_000117.1
ETFA	NM_001127716.2	c.39+7441G>A		intron_variant			NP_001121188.1
ETFA	XR_007064434.1	n.120+7441G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETFA	ENST00000557943.6	c.39+7441G>A		intron_variant		1	NM_000126.4	ENSP00000452762.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39514 AN: 152036 Hom.: 5839 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.265

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.260 AC: 39530 AN: 152152 Hom.: 5846 Cov.: 32 AF XY: 0.267 AC XY: 19870 AN XY: 74378

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.265

Alfa AF: 0.263 Hom.: 2562

Bravo AF: 0.255

Asia WGS AF: 0.518 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs4886791; hg19: chr15-76596250;