6-154244201-G-A

Variant names:

• chr6-154244201-G-A
• rs4314511
• NM_001130700.2:c.246+2390C>T

Variant summary

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

The NM_001130700.2(IPCEF1):​c.246+2390C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,076 control chromosomes in the GnomAD database, including 56,012 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 0.85 (56012 hom., cov: 30)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 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.246+2390C>T		intron	N/A	NP_001124172.1
	IPCEF1	NM_001130699.2		c.246+2390C>T		intron	N/A	NP_001124171.1
	IPCEF1	NM_001394799.1		c.246+2390C>T		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.246+2390C>T		intron	N/A	ENSP00000356189.4
	ENSG00000288520	ENST00000673182.1		c.1629+2390C>T		intron	N/A	ENSP00000499846.1
	IPCEF1	ENST00000422970.6	TSL:1	c.246+2390C>T		intron	N/A	ENSP00000394751.2

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129343 AN: 151958 Hom.: 55963 Cov.: 30

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.851 AC: 129456 AN: 152076 Hom.: 56012 Cov.: 30 AF XY: 0.844 AC XY: 62738 AN XY: 74318

African (AFR) AF: 0.907 AC: 37608 AN: 41470

American (AMR) AF: 0.883 AC: 13492 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3038 AN: 3472

East Asian (EAS) AF: 0.333 AC: 1716 AN: 5150

South Asian (SAS) AF: 0.617 AC: 2979 AN: 4826

European-Finnish (FIN) AF: 0.845 AC: 8924 AN: 10560

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58938 AN: 67996

Other (OTH) AF: 0.851 AC: 1798 AN: 2114

Alfa AF: 0.854 Hom.: 249474

Bravo AF: 0.859

Asia WGS AF: 0.545 AC: 1896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.55
PhyloP100		-0.064
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: rs4314511; hg19: chr6-154565335;