rs10258236

Positions:

• chr7-111468204-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000405709.7(IMMP2L):​c.239+19034A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,096 control chromosomes in the GnomAD database, including 4,548 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 0.18 (4548 hom., cov: 32)
• Consequence: IMMP2L ENST00000405709.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMMP2L	NM_032549.4	c.239+19034A>G		intron_variant		ENST00000405709.7	NP_115938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMMP2L	ENST00000405709.7	c.239+19034A>G		intron_variant		1	NM_032549.4	ENSP00000384966	P1
IMMP2L	ENST00000331762.7	c.239+19034A>G		intron_variant		1		ENSP00000329553	P1
IMMP2L	ENST00000447215.5	c.239+19034A>G		intron_variant		3		ENSP00000388327
IMMP2L	ENST00000452895.5	c.239+19034A>G		intron_variant		5		ENSP00000399353	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26981 AN: 151980 Hom.: 4515 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.178 AC: 27058 AN: 152096 Hom.: 4548 Cov.: 32 AF XY: 0.171 AC XY: 12704 AN XY: 74360

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.0980

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0211

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.0811

Gnomad4 OTH AF: 0.167

Alfa AF: 0.101 Hom.: 1355

Bravo AF: 0.194

Asia WGS AF: 0.0420 AC: 147 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.3
DANN	Benign	0.44

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: rs10258236; hg19: chr7-111108260;