chr6-154220769-C-T

Variant names:

• chr6-154220769-C-T
• rs790266
• NM_001130700.2:c.392+488G>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.392+488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,074 control chromosomes in the GnomAD database, including 16,945 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 0.47 (16945 hom., cov: 33)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPCEF1	NM_001130700.2	c.392+488G>A		intron_variant	Intron 7 of 11	ENST00000367220.9	NP_001124172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPCEF1	ENST00000367220.9	c.392+488G>A		intron_variant	Intron 7 of 11	2	NM_001130700.2	ENSP00000356189.4
ENSG00000288520	ENST00000673182.1	c.1775+488G>A		intron_variant	Intron 17 of 21			ENSP00000499846.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71092 AN: 151956 Hom.: 16928 Cov.: 33

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.468 AC: 71148 AN: 152074 Hom.: 16945 Cov.: 33 AF XY: 0.468 AC XY: 34814 AN XY: 74352

African (AFR) AF: 0.469 AC: 19424 AN: 41458

American (AMR) AF: 0.576 AC: 8812 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1208 AN: 3464

East Asian (EAS) AF: 0.299 AC: 1551 AN: 5182

South Asian (SAS) AF: 0.497 AC: 2395 AN: 4820

European-Finnish (FIN) AF: 0.451 AC: 4764 AN: 10566

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31664 AN: 67970

Other (OTH) AF: 0.459 AC: 967 AN: 2108

Alfa AF: 0.473 Hom.: 4908

Bravo AF: 0.473

Asia WGS AF: 0.431 AC: 1497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-0.22
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: rs790266; hg19: chr6-154541903;