rs1914816

Variant names:

• chr15-76254592-G-A
• rs1914816
• NM_000126.4:c.816+19820C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• multiple acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ETFA	NM_000126.4	c.816+19820C>T		intron_variant	Intron 9 of 11	ENST00000557943.6	NP_000117.1
ETFA	NM_001127716.2	c.669+19820C>T		intron_variant	Intron 8 of 10		NP_001121188.1
ETFA	XR_007064434.1	n.897+19820C>T		intron_variant	Intron 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETFA	ENST00000557943.6	c.816+19820C>T		intron_variant	Intron 9 of 11	1	NM_000126.4	ENSP00000452762.1

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

African (AFR) AF: 0.353 AC: 14614 AN: 41432

American (AMR) AF: 0.158 AC: 2411 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3468

East Asian (EAS) AF: 0.0539 AC: 279 AN: 5174

South Asian (SAS) AF: 0.128 AC: 615 AN: 4818

European-Finnish (FIN) AF: 0.203 AC: 2140 AN: 10566

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12541 AN: 67986

Other (OTH) AF: 0.207 AC: 437 AN: 2112

Alfa AF: 0.194 Hom.: 6000

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
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1914816; hg19: chr15-76546933;