6-154166842-C-T

Variant names:

• chr6-154166842-C-T
• rs6941251
• NM_001130700.2:c.1104+1078G>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.1104+1078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,090 control chromosomes in the GnomAD database, including 30,024 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 0.62 (30024 hom., cov: 33)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 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.1104+1078G>A		intron	N/A	NP_001124172.1	Q8WWN9-2
	IPCEF1	NM_001130699.2		c.1104+1078G>A		intron	N/A	NP_001124171.1	Q8WWN9-2
	IPCEF1	NM_001394799.1		c.1104+1078G>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.1104+1078G>A		intron	N/A	ENSP00000356189.4	Q8WWN9-2
	ENSG00000288520	ENST00000673182.1		c.2487+1078G>A		intron	N/A	ENSP00000499846.1
	IPCEF1	ENST00000422970.6	TSL:1	c.1104+1078G>A		intron	N/A	ENSP00000394751.2	Q8WWN9-2

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94308 AN: 151972 Hom.: 29994 Cov.: 33

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.621 AC: 94379 AN: 152090 Hom.: 30024 Cov.: 33 AF XY: 0.616 AC XY: 45756 AN XY: 74338

African (AFR) AF: 0.738 AC: 30628 AN: 41480

American (AMR) AF: 0.482 AC: 7360 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2455 AN: 3472

East Asian (EAS) AF: 0.711 AC: 3675 AN: 5170

South Asian (SAS) AF: 0.479 AC: 2309 AN: 4818

European-Finnish (FIN) AF: 0.578 AC: 6103 AN: 10552

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39754 AN: 67992

Other (OTH) AF: 0.633 AC: 1339 AN: 2116

Alfa AF: 0.588 Hom.: 14563

Bravo AF: 0.623

Asia WGS AF: 0.588 AC: 2044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.49
PhyloP100		-0.0080
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: rs6941251; hg19: chr6-154487977;