12-25197188-T-C

Variant names:

• chr12-25197188-T-C
• rs7137734
• NM_001001660.3:c.-38+1851T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001660.3(ETFRF1):​c.-38+1851T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,758 control chromosomes in the GnomAD database, including 5,032 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 0.25 (5032 hom., cov: 31)
• Consequence: ETFRF1 NM_001001660.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETFRF1	NM_001001660.3	MANE Select	c.-38+1851T>C		intron	N/A	NP_001001660.2	Q6IPR1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETFRF1	ENST00000381356.9	TSL:1 MANE Select	c.-38+1851T>C		intron	N/A	ENSP00000370761.4	Q6IPR1
	ETFRF1	ENST00000556351.6	TSL:2	c.-146+1851T>C		intron	N/A	ENSP00000452146.2	Q6IPR1
	ETFRF1	ENST00000556927.6	TSL:3	c.-137+1851T>C		intron	N/A	ENSP00000450443.2	Q6IPR1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37271 AN: 151640 Hom.: 5017 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.246 AC: 37305 AN: 151758 Hom.: 5032 Cov.: 31 AF XY: 0.246 AC XY: 18244 AN XY: 74158

African (AFR) AF: 0.148 AC: 6104 AN: 41364

American (AMR) AF: 0.356 AC: 5429 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3470

East Asian (EAS) AF: 0.360 AC: 1854 AN: 5156

South Asian (SAS) AF: 0.295 AC: 1418 AN: 4804

European-Finnish (FIN) AF: 0.200 AC: 2095 AN: 10492

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18469 AN: 67930

Other (OTH) AF: 0.269 AC: 564 AN: 2100

Alfa AF: 0.262 Hom.: 8336

Bravo AF: 0.251

Asia WGS AF: 0.383 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.94
DANN	Benign	0.65
PhyloP100		-0.28
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: rs7137734; hg19: chr12-25350122;