rs1223118

Positions:

• chr11-31448953-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001304274.2(IMMP1L):​c.321+7307C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 985,216 control chromosomes in the GnomAD database, including 2,314 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 0.088 (1636 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (678 hom.)
• Consequence: IMMP1L NM_001304274.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

Genes affected

IMMP1L (HGNC:26317): (inner mitochondrial membrane peptidase subunit 1) The mitochondrial inner membrane peptidase (IMP) complex generates mature, active proteins in the mitochondrial intermembrane space by proteolytically removing the mitochondrial targeting presequence of nuclear-encoded proteins. IMP1 and IMP2 (IMMP2L; MIM 605977) are the catalytic subunits of the IMP complex (Burri et al., 2005 [PubMed 15814844]).[supplied by OMIM, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMMP1L	NM_001304274.2	c.321+7307C>G		intron_variant		ENST00000532287.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMMP1L	ENST00000532287.6	c.321+7307C>G		intron_variant		1	NM_001304274.2	P1

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13404 AN: 152042 Hom.: 1629 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00265

Gnomad OTH AF: 0.0690

GnomAD4 exome AF: 0.00830 AC: 6914 AN: 833056 Hom.: 678 Cov.: 30 AF XY: 0.00768 AC XY: 2953 AN XY: 384688

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.00311

Gnomad4 EAS exome AF: 0.0275

Gnomad4 SAS exome AF: 0.00182

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00216

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0884 AC: 13458 AN: 152160 Hom.: 1636 Cov.: 32 AF XY: 0.0861 AC XY: 6406 AN XY: 74394

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.0239

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00265

Gnomad4 OTH AF: 0.0683

Alfa AF: 0.0537 Hom.: 116

Bravo AF: 0.108

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.63

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: rs1223118; hg19: chr11-31470500;