11-31448953-G-C

Variant names:

• chr11-31448953-G-C
• rs1223118
• NM_001304274.2:c.321+7307C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304274.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMMP1L	NM_001304274.2	MANE Select	c.321+7307C>G		intron	N/A	NP_001291203.1
	IMMP1L	NM_144981.3		c.321+7307C>G		intron	N/A	NP_659418.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMMP1L	ENST00000532287.6	TSL:1 MANE Select	c.321+7307C>G		intron	N/A	ENSP00000435576.1
	IMMP1L	ENST00000648582.1		n.*85C>G		non_coding_transcript_exon	Exon 7 of 9	ENSP00000497019.1
	IMMP1L	ENST00000648582.1		n.*85C>G		3_prime_UTR	Exon 7 of 9	ENSP00000497019.1

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

African (AFR) AF: 0.283 AC: 4455 AN: 15760

American (AMR) AF: 0.118 AC: 116 AN: 980

Ashkenazi Jewish (ASJ) AF: 0.00311 AC: 16 AN: 5152

East Asian (EAS) AF: 0.0275 AC: 100 AN: 3630

South Asian (SAS) AF: 0.00182 AC: 30 AN: 16456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 280

Middle Eastern (MID) AF: 0.0228 AC: 37 AN: 1620

European-Non Finnish (NFE) AF: 0.00216 AC: 1644 AN: 761884

Other (OTH) AF: 0.0189 AC: 516 AN: 27294

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

African (AFR) AF: 0.270 AC: 11190 AN: 41472

American (AMR) AF: 0.117 AC: 1784 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3468

East Asian (EAS) AF: 0.0239 AC: 124 AN: 5182

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00265 AC: 180 AN: 68006

Other (OTH) AF: 0.0683 AC: 144 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.63
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1223118; hg19: chr11-31470500;