rs12537269

Variant names:

• chr7-110757491-G-A
• rs12537269
• NM_032549.4:c.409-93770C>T

Variant summary

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

The NM_032549.4(IMMP2L):​c.409-93770C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,980 control chromosomes in the GnomAD database, including 3,549 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 (3549 hom., cov: 32)
• Consequence: IMMP2L NM_032549.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMMP2L	NM_032549.4	c.409-93770C>T		intron_variant	Intron 5 of 5	ENST00000405709.7	NP_115938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMMP2L	ENST00000405709.7	c.409-93770C>T		intron_variant	Intron 5 of 5	1	NM_032549.4	ENSP00000384966.2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32236 AN: 151862 Hom.: 3546 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.212 AC: 32256 AN: 151980 Hom.: 3549 Cov.: 32 AF XY: 0.215 AC XY: 15942 AN XY: 74282

African (AFR) AF: 0.185 AC: 7661 AN: 41472

American (AMR) AF: 0.234 AC: 3572 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3468

East Asian (EAS) AF: 0.120 AC: 618 AN: 5144

South Asian (SAS) AF: 0.325 AC: 1562 AN: 4808

European-Finnish (FIN) AF: 0.244 AC: 2576 AN: 10574

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14737 AN: 67950

Other (OTH) AF: 0.211 AC: 446 AN: 2110

Alfa AF: 0.218 Hom.: 2935

Bravo AF: 0.210

Asia WGS AF: 0.252 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.83
PhyloP100		-0.49
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: rs12537269; hg19: chr7-110397547;