Genetic Variant IMMP1L:c.-64T>C (chr11-31509553-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001304274.2(IMMP1L):c.-64T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 572,860 control chromosomes in the GnomAD database, including 19,534 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 0.26 ( 5588 hom., cov: 32)

Exomes 𝑓: 0.25 ( 13946 hom. )

Consequence

IMMP1L
NM_001304274.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.708

Variant links:

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]

IMMP1L links:

ELP4 (HGNC:1171): (elongator acetyltransferase complex subunit 4) This gene encodes a component of the six subunit elongator complex, a histone acetyltransferase complex that associates directly with RNA polymerase II during transcriptional elongation. The human gene can partially complement sensitivity phenotypes of yeast ELP4 deletion mutants. This gene has also been associated with Rolandic epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ELP4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMMP1L	NM_001304274.2 link	c.-64T>C		5_prime_UTR_variant	Exon 1 of 6	ENST00000532287.6	NP_001291203.1	Q96LU5
ELP4	NM_019040.5 link	c.-232A>G		upstream_gene_variant		ENST00000640961.2	NP_061913.3	Q96EB1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMMP1L	ENST00000532287.6 link	c.-64T>C		5_prime_UTR_variant	Exon 1 of 6	1	NM_001304274.2	ENSP00000435576.1		Q96LU5
ELP4	ENST00000640961.2 link	c.-232A>G		upstream_gene_variant		1	NM_019040.5	ENSP00000492152.1		Q96EB1-1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40161

AN:

151970

Hom.:

5574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.288

GnomAD4 exome

AF:

0.251

AC:

105428

AN:

420772

Hom.:

13946

Cov.:

AF XY:

0.256

AC XY:

56250

AN XY:

220078

show subpopulations

Gnomad4 AFR exome

AF:

0.343

Gnomad4 AMR exome

AF:

0.240

Gnomad4 ASJ exome

AF:

0.296

Gnomad4 EAS exome

AF:

0.304

Gnomad4 SAS exome

AF:

0.337

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.253

GnomAD4 genome

AF:

0.264

AC:

40198

AN:

152088

Hom.:

5588

Cov.:

AF XY:

0.261

AC XY:

19388

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.336

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.304

Gnomad4 EAS

AF:

0.293

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.236

Gnomad4 OTH

AF:

0.298

Alfa

AF:

0.0841

Hom.:

113

Bravo

AF:

0.275

Asia WGS

AF:

0.343

AC:

1191

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.96

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over