rs1914816

Positions:

• chr15-76254592-G-A
• chr15-76254592-G-T

Variant summary

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

The NM_000126.4(ETFA):​c.816+19820C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,038 control chromosomes in the GnomAD database, including 4,393 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 0.22 (4393 hom., cov: 32)
• Consequence: ETFA NM_000126.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETFA	NM_000126.4	c.816+19820C>T		intron_variant		ENST00000557943.6
ETFA	NM_001127716.2	c.669+19820C>T		intron_variant
ETFA	XR_007064434.1	n.897+19820C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETFA	ENST00000557943.6	c.816+19820C>T		intron_variant		1	NM_000126.4	P1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33775 AN: 151920 Hom.: 4378 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.223 AC: 33830 AN: 152038 Hom.: 4393 Cov.: 32 AF XY: 0.222 AC XY: 16514 AN XY: 74332

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.0539

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.207

Alfa AF: 0.158 Hom.: 701

Bravo AF: 0.224

Asia WGS AF: 0.121 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.5
DANN	Benign	0.84

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: rs1914816; hg19: chr15-76546933;