6-154185294-A-G

Variant names:

• chr6-154185294-A-G
• rs1998220
• NM_001130700.2:c.910+14374T>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.910+14374T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,062 control chromosomes in the GnomAD database, including 30,454 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 (30454 hom., cov: 32)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 8 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 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.910+14374T>C		intron	N/A	NP_001124172.1
	IPCEF1	NM_001130699.2		c.910+14374T>C		intron	N/A	NP_001124171.1
	IPCEF1	NM_001394799.1		c.910+14374T>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.910+14374T>C		intron	N/A	ENSP00000356189.4
	ENSG00000288520	ENST00000673182.1		c.2293+14374T>C		intron	N/A	ENSP00000499846.1
	IPCEF1	ENST00000422970.6	TSL:1	c.910+14374T>C		intron	N/A	ENSP00000394751.2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94946 AN: 151944 Hom.: 30420 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.625 AC: 95021 AN: 152062 Hom.: 30454 Cov.: 32 AF XY: 0.619 AC XY: 46004 AN XY: 74324

African (AFR) AF: 0.755 AC: 31334 AN: 41492

American (AMR) AF: 0.483 AC: 7371 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2454 AN: 3468

East Asian (EAS) AF: 0.706 AC: 3660 AN: 5184

South Asian (SAS) AF: 0.484 AC: 2333 AN: 4818

European-Finnish (FIN) AF: 0.575 AC: 6077 AN: 10574

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39706 AN: 67950

Other (OTH) AF: 0.631 AC: 1333 AN: 2112

Alfa AF: 0.522 Hom.: 2780

Bravo AF: 0.629

Asia WGS AF: 0.585 AC: 2033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.45
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: rs1998220; hg19: chr6-154506428;