rs4963857

Variant names:

• chr12-25203466-G-A
• rs4963857
• NM_001001660.3:c.-37-454G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-25203466-G-A
• chr12-25203466-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001660.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETFRF1	NM_001001660.3	MANE Select	c.-37-454G>A		intron	N/A	NP_001001660.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETFRF1	ENST00000381356.9	TSL:1 MANE Select	c.-37-454G>A		intron	N/A	ENSP00000370761.4
	ETFRF1	ENST00000878638.1		c.-491G>A		5_prime_UTR	Exon 1 of 2	ENSP00000548697.1
	ETFRF1	ENST00000556351.6	TSL:2	c.-145-259G>A		intron	N/A	ENSP00000452146.2

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

African (AFR) AF: 0.0170 AC: 707 AN: 41574

American (AMR) AF: 0.0542 AC: 829 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0528 AC: 183 AN: 3466

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.0843 AC: 406 AN: 4818

European-Finnish (FIN) AF: 0.226 AC: 2388 AN: 10578

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7182 AN: 68014

Other (OTH) AF: 0.0596 AC: 126 AN: 2114

Alfa AF: 0.0774 Hom.: 352

Bravo AF: 0.0624

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.56
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs4963857; hg19: chr12-25356400;