rs11047887

chr12-25195738-A-Cchr12-25195738-A-G

Variant summary

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

The NM_001001660.3(ETFRF1):c.-38+401A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,430 control chromosomes in the GnomAD database, including 16,980 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 0.44 (16953 hom., cov: 32)
  • Exomes 𝑓: 0.39 (27 hom.)
• Consequence: ETFRF1 NM_001001660.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETFRF1	NM_001001660.3	c.-38+401A>C		intron_variant		ENST00000381356.9
ETFRF1	XM_017018850.3	c.-8132A>C		5_prime_UTR_variant	1/3
ETFRF1	XM_005253319.5	c.-38+397A>C		intron_variant
ETFRF1	XM_005253320.5	c.-146+401A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETFRF1	ENST00000381356.9	c.-38+401A>C		intron_variant		1	NM_001001660.3	P1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67584 AN: 151982 Hom.: 16952 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.394 AC: 130 AN: 330 Hom.: 27 Cov.: 0 AF XY: 0.446 AC XY: 91 AN XY: 204

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.408

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.411

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.444 AC: 67604 AN: 152100 Hom.: 16953 Cov.: 32 AF XY: 0.449 AC XY: 33374 AN XY: 74348

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.463

Alfa AF: 0.509 Hom.: 25716

Bravo AF: 0.430

Asia WGS AF: 0.652 AC: 2266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.1
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs11047887; hg19: chr12-25348672;