rs790259

Positions:

• chr6-154217225-A-G

Variant summary

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

The NM_001130700.2(IPCEF1):​c.393-2949T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 162,604 control chromosomes in the GnomAD database, including 21,837 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 0.52 (20978 hom., cov: 31)
  • Exomes 𝑓: 0.40 (859 hom.)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

Genes affected

IPCEF1 (HGNC:21204): (interaction protein for cytohesin exchange factors 1) Predicted to enable peroxidase activity. Predicted to be involved in response to oxidative stress. Predicted to be located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

OPRM1 (HGNC:8156): (opioid receptor mu 1) This gene encodes one of at least three opioid receptors in humans; the mu opioid receptor (MOR). The MOR is the principal target of endogenous opioid peptides and opioid analgesic agents such as beta-endorphin and enkephalins. The MOR also has an important role in dependence to other drugs of abuse, such as nicotine, cocaine, and alcohol via its modulation of the dopamine system. The NM_001008503.2:c.118A>G allele has been associated with opioid and alcohol addiction and variations in pain sensitivity but evidence for it having a causal role is conflicting. Multiple transcript variants encoding different isoforms have been found for this gene. Though the canonical MOR belongs to the superfamily of 7-transmembrane-spanning G-protein-coupled receptors some isoforms of this gene have only 6 transmembrane domains. [provided by RefSeq, Oct 2013]

RPL17P24 (HGNC:36506): (ribosomal protein L17 pseudogene 24)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPCEF1	NM_001130700.2	c.393-2949T>C		intron_variant		ENST00000367220.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPCEF1	ENST00000367220.9	c.393-2949T>C		intron_variant		2	NM_001130700.2	A2
RPL17P24	ENST00000456309.1	n.295A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78165 AN: 151814 Hom.: 20937 Cov.: 31

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.397 AC: 4235 AN: 10672 Hom.: 859 Cov.: 0 AF XY: 0.387 AC XY: 2481 AN XY: 6404

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.604

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.515 AC: 78260 AN: 151932 Hom.: 20978 Cov.: 31 AF XY: 0.515 AC XY: 38226 AN XY: 74246

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.494

Alfa AF: 0.527 Hom.: 4072

Bravo AF: 0.528

Asia WGS AF: 0.476 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.3
DANN	Benign	0.69

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: rs790259; hg19: chr6-154538359;