rs78201564

Variant names:

• chr4-158672031-A-C
• rs78201564
• ENST00000508836.1:n.225T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-158672031-A-C
• chr4-158672031-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000908056.1(ETFDH):​c.-284A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 398,508 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: ETFDH ENST00000908056.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 0 publications found

Genes affected

C4orf46 (HGNC:27320): (chromosome 4 open reading frame 46) This gene encodes a small, conserved protein of unknown function that is expressed in a variety of tissues. There are pseudogenes for this gene on chromosomes 6, 8, 16, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]

ETFDH (HGNC:3483): (electron transfer flavoprotein dehydrogenase) This gene encodes a component of the electron-transfer system in mitochondria and is essential for electron transfer from a number of mitochondrial flavin-containing dehydrogenases to the main respiratory chain. Mutations in this gene are associated with glutaric acidemia. Alternatively spliced transcript variants that encode distinct isoforms have been observed. [provided by RefSeq, Aug 2013]

ETFDH Gene-Disease associations (from GenCC):

• multiple acyl-CoA dehydrogenase deficiency

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000908056.1. 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
	C4orf46	NR_077234.2		n.26T>G		non_coding_transcript_exon	Exon 1 of 2
	C4orf46	NR_077235.2		n.26T>G		non_coding_transcript_exon	Exon 1 of 2
	C4orf46	NM_001008393.4	MANE Select	c.-230T>G		upstream_gene	N/A	NP_001008394.1	Q504U0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4orf46	ENST00000508836.1	TSL:1	n.225T>G		non_coding_transcript_exon	Exon 1 of 2
	ETFDH	ENST00000908056.1		c.-284A>C		5_prime_UTR	Exon 1 of 14	ENSP00000578115.1
	ETFDH	ENST00000512251.6	TSL:4	n.64A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000251 AC: 1 AN: 398508 Hom.: 0 Cov.: 3 AF XY: 0.00000481 AC XY: 1 AN XY: 207872

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11376

American (AMR) AF: 0.00 AC: 0 AN: 15598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12580

East Asian (EAS) AF: 0.00 AC: 0 AN: 28634

South Asian (SAS) AF: 0.00 AC: 0 AN: 35480

European-Finnish (FIN) AF: 0.0000359 AC: 1 AN: 27854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1786

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 241586

Other (OTH) AF: 0.00 AC: 0 AN: 23614

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		-0.31
PromoterAI		0.0094	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs78201564; hg19: chr4-159593183;