11-31509553-A-G

Variant names:

• chr11-31509553-A-G
• rs2295748
• ENST00000528161.5:n.11T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000528161.5(IMMP1L):​n.11T>C variant causes a non coding transcript exon 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 ENST00000528161.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 9 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]

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 Gene-Disease associations (from GenCC):

• aniridia 2

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Genomics England PanelApp
• aniridia 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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	c.-64T>C		5_prime_UTR_variant	Exon 1 of 6	ENST00000532287.6	NP_001291203.1
ELP4	NM_019040.5	c.-232A>G		upstream_gene_variant		ENST00000640961.2	NP_061913.3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40161 AN: 151970 Hom.: 5574 Cov.: 32

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.: 3 AF XY: 0.256 AC XY: 56250 AN XY: 220078

African (AFR) AF: 0.343 AC: 4109 AN: 11994

American (AMR) AF: 0.240 AC: 4296 AN: 17930

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 3849 AN: 13020

East Asian (EAS) AF: 0.304 AC: 8894 AN: 29224

South Asian (SAS) AF: 0.337 AC: 14353 AN: 42626

European-Finnish (FIN) AF: 0.138 AC: 3765 AN: 27314

Middle Eastern (MID) AF: 0.283 AC: 517 AN: 1828

European-Non Finnish (NFE) AF: 0.236 AC: 59396 AN: 252156

Other (OTH) AF: 0.253 AC: 6249 AN: 24680

GnomAD4 genome AF: 0.264 AC: 40198 AN: 152088 Hom.: 5588 Cov.: 32 AF XY: 0.261 AC XY: 19388 AN XY: 74342

African (AFR) AF: 0.336 AC: 13933 AN: 41482

American (AMR) AF: 0.254 AC: 3888 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1053 AN: 3466

East Asian (EAS) AF: 0.293 AC: 1512 AN: 5158

South Asian (SAS) AF: 0.340 AC: 1633 AN: 4810

European-Finnish (FIN) AF: 0.116 AC: 1236 AN: 10610

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16045 AN: 67970

Other (OTH) AF: 0.298 AC: 628 AN: 2110

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
PhyloP100		-0.71
PromoterAI		-0.012	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2295748; hg19: chr11-31531100;