rs738288

Positions:

• chr22-39511656-G-A
• chr22-39511656-G-C
• chr22-39511656-G-T

Variant summary

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

The NM_019008.6(MIEF1):​c.145-193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,140 control chromosomes in the GnomAD database, including 30,393 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 0.62 (30393 hom., cov: 34)
• Consequence: MIEF1 NM_019008.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

Genes affected

MIEF1 (HGNC:25979): (mitochondrial elongation factor 1) Enables ADP binding activity; GDP binding activity; and identical protein binding activity. Involved in several processes, including positive regulation of mitochondrial fission; positive regulation of mitochondrial translation; and positive regulation of protein targeting to membrane. Located in mitochondrial matrix and mitochondrial outer membrane. Colocalizes with mitochondrial large ribosomal subunit. [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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIEF1	NM_019008.6	c.145-193G>A		intron_variant		ENST00000325301.7
MIEF1	NM_001304564.2	c.145-193G>A		intron_variant
MIEF1	NR_130789.2	n.632-193G>A		intron_variant, non_coding_transcript_variant
MIEF1	NR_130790.2	n.782-193G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIEF1	ENST00000325301.7	c.145-193G>A		intron_variant		1	NM_019008.6	P1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94817 AN: 152022 Hom.: 30358 Cov.: 34

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.624 AC: 94896 AN: 152140 Hom.: 30393 Cov.: 34 AF XY: 0.629 AC XY: 46756 AN XY: 74370

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.651

Alfa AF: 0.550 Hom.: 12574

Bravo AF: 0.629

Asia WGS AF: 0.834 AC: 2898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.76

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: rs738288; hg19: chr22-39907661;