rs4963857

chr12-25203466-G-Achr12-25203466-G-T

Variant summary

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

The NM_001001660.3(ETFRF1):c.-37-454G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 152,258 control chromosomes in the GnomAD database, including 716 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 0.078 (716 hom., cov: 32)
• Consequence: ETFRF1 NM_001001660.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201

Genes affected

ETFRF1 (HGNC:27052): (electron transfer flavoprotein regulatory factor 1) Involved in respiratory electron transport chain. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

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 (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETFRF1	NM_001001660.3	c.-37-454G>A		intron_variant		ENST00000381356.9
ETFRF1	XM_017018850.3	c.-404G>A		5_prime_UTR_variant	1/3
ETFRF1	XM_005253319.5	c.-37-454G>A		intron_variant
ETFRF1	XM_005253320.5	c.-145-259G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETFRF1	ENST00000381356.9	c.-37-454G>A		intron_variant		1	NM_001001660.3	P1

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11880 AN: 152140 Hom.: 716 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0543

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0602

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

GnomAD4 genome AF: 0.0780 AC: 11875 AN: 152258 Hom.: 716 Cov.: 32 AF XY: 0.0827 AC XY: 6156 AN XY: 74412

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0542

Gnomad4 ASJ AF: 0.0528

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0843

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0596

Alfa AF: 0.0873 Hom.: 313

Bravo AF: 0.0624

Asia WGS AF: 0.0330 AC: 117 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	5.5
Dann	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs4963857; hg19: chr12-25356400;