12-25197188-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) 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
ETFRF1	NM_001001660.3	c.-38+1851T>C		intron_variant	Intron 1 of 2	ENST00000381356.9	NP_001001660.2
ETFRF1	XM_017018850.3	c.-6682T>C		5_prime_UTR_variant	Exon 1 of 3		XP_016874339.1
ETFRF1	XM_005253319.5	c.-38+1847T>C		intron_variant	Intron 1 of 2		XP_005253376.1
ETFRF1	XM_005253320.5	c.-146+1851T>C		intron_variant	Intron 1 of 3		XP_005253377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETFRF1	ENST00000381356.9	c.-38+1851T>C		intron_variant	Intron 1 of 2	1	NM_001001660.3	ENSP00000370761.4

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

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.269

Alfa AF: 0.262 Hom.: 5824

Bravo AF: 0.251

Asia WGS AF: 0.383 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.94
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs7137734; hg19: chr12-25350122;