rs1464895

Positions:

• chr7-110684685-C-T

Variant summary

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

The NM_032549.4(IMMP2L):​c.409-20964G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,756 control chromosomes in the GnomAD database, including 4,105 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 0.21 (4105 hom., cov: 32)
• Consequence: IMMP2L NM_032549.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMMP2L	NM_032549.4	c.409-20964G>A		intron_variant		ENST00000405709.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMMP2L	ENST00000405709.7	c.409-20964G>A		intron_variant		1	NM_032549.4	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32466 AN: 151638 Hom.: 4103 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.214 AC: 32504 AN: 151756 Hom.: 4105 Cov.: 32 AF XY: 0.215 AC XY: 15941 AN XY: 74118

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.213

Alfa AF: 0.171 Hom.: 4755

Bravo AF: 0.220

Asia WGS AF: 0.264 AC: 916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.69

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: rs1464895; hg19: chr7-110324741;