rs1528039

Positions:

• chr7-110802716-A-G
• chr7-110802716-A-T

Variant summary

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

The NM_032549.4(IMMP2L):​c.408+83877T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,928 control chromosomes in the GnomAD database, including 5,063 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 0.25 (5063 hom., cov: 31)
• Consequence: IMMP2L NM_032549.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81

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=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMMP2L	NM_032549.4	c.408+83877T>C		intron_variant		ENST00000405709.7	NP_115938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMMP2L	ENST00000405709.7	c.408+83877T>C		intron_variant		1	NM_032549.4	ENSP00000384966	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37537 AN: 151810 Hom.: 5059 Cov.: 31

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.247 AC: 37572 AN: 151928 Hom.: 5063 Cov.: 31 AF XY: 0.250 AC XY: 18548 AN XY: 74250

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.244

Alfa AF: 0.210 Hom.: 1807

Bravo AF: 0.248

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	-0.56
CADD	Benign	13
DANN	Benign	0.80

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: rs1528039; hg19: chr7-110442772; COSMIC: COSV59277182;