rs2605141

Positions:

• chr17-18260925-T-C

Variant summary

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

The NM_139162.4(MIEF2):​c.-8+188T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,108 control chromosomes in the GnomAD database, including 39,916 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 0.72 (39916 hom., cov: 33)
• Consequence: MIEF2 NM_139162.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

Genes affected

MIEF2 (HGNC:17920): (mitochondrial elongation factor 2) This gene encodes an outer mitochondrial membrane protein that functions in the regulation of mitochondrial morphology. It can directly recruit the fission mediator dynamin-related protein 1 (Drp1) to the mitochondrial surface. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

MIEF2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIEF2	NM_139162.4	c.-8+188T>C		intron_variant		ENST00000323019.9	NP_631901.2
MIEF2	XM_017024190.2	c.-789T>C		5_prime_UTR_variant	1/4		XP_016879679.1
MIEF2	NM_001144900.3	c.-8+188T>C		intron_variant			NP_001138372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIEF2	ENST00000323019.9	c.-8+188T>C		intron_variant		2	NM_139162.4	ENSP00000323591.4

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109103 AN: 151990 Hom.: 39868 Cov.: 33

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.718 AC: 109217 AN: 152108 Hom.: 39916 Cov.: 33 AF XY: 0.714 AC XY: 53107 AN XY: 74348

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.702

Alfa AF: 0.712 Hom.: 5609

Bravo AF: 0.722

Asia WGS AF: 0.543 AC: 1891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.2
DANN	Benign	0.57

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: rs2605141; hg19: chr17-18164239;