rs214475

Positions:

• chr7-111227479-A-G

Variant summary

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

The NM_032549.4(IMMP2L):​c.239+259759T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,916 control chromosomes in the GnomAD database, including 31,696 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 0.64 (31696 hom., cov: 31)
• Consequence: IMMP2L NM_032549.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

Genes affected

IMMP2L (HGNC:14598): (inner mitochondrial membrane peptidase subunit 2) This gene encodes a protein involved in processing the signal peptide sequences used to direct mitochondrial proteins to the mitochondria. The encoded protein resides in the mitochondria and is one of the necessary proteins for the catalytic activity of the mitochondrial inner membrane peptidase (IMP) complex. Two variants that encode the same protein have been described for this gene. [provided by RefSeq, Sep 2011]

LOC124901725 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMMP2L	NM_032549.4	c.239+259759T>C		intron_variant		ENST00000405709.7
LOC124901725	XR_007060477.1	n.16084T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMMP2L	ENST00000405709.7	c.239+259759T>C		intron_variant		1	NM_032549.4	P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97421 AN: 151798 Hom.: 31677 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.642 AC: 97489 AN: 151916 Hom.: 31696 Cov.: 31 AF XY: 0.633 AC XY: 47022 AN XY: 74244

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.601

Alfa AF: 0.650 Hom.: 56253

Bravo AF: 0.643

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.71

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: rs214475; hg19: chr7-110867535;