chr6-154161032-C-T

Variant names:

• chr6-154161032-C-T
• rs1918760
• NM_001130700.2:c.1105-992G>A

Variant summary

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

The NM_001130700.2(IPCEF1):​c.1105-992G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,930 control chromosomes in the GnomAD database, including 34,688 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 0.67 (34688 hom., cov: 30)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPCEF1	NM_001130700.2	MANE Select	c.1105-992G>A		intron	N/A	NP_001124172.1	Q8WWN9-2
	IPCEF1	NM_001130699.2		c.1105-992G>A		intron	N/A	NP_001124171.1	Q8WWN9-2
	IPCEF1	NM_001394799.1		c.1105-992G>A		intron	N/A	NP_001381728.1	Q8WWN9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPCEF1	ENST00000367220.9	TSL:2 MANE Select	c.1105-992G>A		intron	N/A	ENSP00000356189.4	Q8WWN9-2
	ENSG00000288520	ENST00000673182.1		c.2488-992G>A		intron	N/A	ENSP00000499846.1
	IPCEF1	ENST00000422970.6	TSL:1	c.1105-992G>A		intron	N/A	ENSP00000394751.2	Q8WWN9-2

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101630 AN: 151812 Hom.: 34649 Cov.: 30

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.669 AC: 101715 AN: 151930 Hom.: 34688 Cov.: 30 AF XY: 0.668 AC XY: 49634 AN XY: 74266

African (AFR) AF: 0.762 AC: 31561 AN: 41424

American (AMR) AF: 0.508 AC: 7746 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2620 AN: 3472

East Asian (EAS) AF: 0.893 AC: 4607 AN: 5160

South Asian (SAS) AF: 0.673 AC: 3243 AN: 4816

European-Finnish (FIN) AF: 0.645 AC: 6797 AN: 10546

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42933 AN: 67934

Other (OTH) AF: 0.678 AC: 1431 AN: 2110

Alfa AF: 0.640 Hom.: 36614

Bravo AF: 0.666

Asia WGS AF: 0.768 AC: 2671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.099
DANN	Benign	0.36
PhyloP100		-2.2
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: rs1918760; hg19: chr6-154482167;