rs790259

Variant names:

• chr6-154217225-A-G
• rs790259
• NM_001130700.2:c.393-2949T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ENSG00000288520 (HGNC:):

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130700.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPCEF1	NM_001130700.2	MANE Select	c.393-2949T>C		intron	N/A	NP_001124172.1
	IPCEF1	NM_001130699.2		c.393-2949T>C		intron	N/A	NP_001124171.1
	IPCEF1	NM_001394799.1		c.393-2949T>C		intron	N/A	NP_001381728.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPCEF1	ENST00000367220.9	TSL:2 MANE Select	c.393-2949T>C		intron	N/A	ENSP00000356189.4
	ENSG00000288520	ENST00000673182.1		c.1776-2949T>C		intron	N/A	ENSP00000499846.1
	IPCEF1	ENST00000422970.6	TSL:1	c.393-2949T>C		intron	N/A	ENSP00000394751.2

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

African (AFR) AF: 0.599 AC: 211 AN: 352

American (AMR) AF: 0.604 AC: 492 AN: 814

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 67 AN: 240

East Asian (EAS) AF: 0.237 AC: 223 AN: 942

South Asian (SAS) AF: 0.442 AC: 425 AN: 962

European-Finnish (FIN) AF: 0.417 AC: 465 AN: 1114

Middle Eastern (MID) AF: 0.313 AC: 5 AN: 16

European-Non Finnish (NFE) AF: 0.379 AC: 2162 AN: 5706

Other (OTH) AF: 0.352 AC: 185 AN: 526

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

African (AFR) AF: 0.644 AC: 26692 AN: 41420

American (AMR) AF: 0.594 AC: 9073 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1223 AN: 3466

East Asian (EAS) AF: 0.312 AC: 1610 AN: 5156

South Asian (SAS) AF: 0.501 AC: 2418 AN: 4822

European-Finnish (FIN) AF: 0.445 AC: 4686 AN: 10542

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31130 AN: 67946

Other (OTH) AF: 0.494 AC: 1041 AN: 2106

Alfa AF: 0.530 Hom.: 4248

Bravo AF: 0.528

Asia WGS AF: 0.476 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.3
DANN	Benign	0.69
PhyloP100		-1.8
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: rs790259; hg19: chr6-154538359;