NM_001130700.2:c.246+1304C>T

Variant names:

• chr6-154245287-G-A
• rs1554817
• NM_001130700.2:c.246+1304C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001130700.2(IPCEF1):​c.246+1304C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.60 (14554 hom., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPCEF1	NM_001130700.2	c.246+1304C>T		intron_variant	Intron 5 of 11	ENST00000367220.9	NP_001124172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPCEF1	ENST00000367220.9	c.246+1304C>T		intron_variant	Intron 5 of 11	2	NM_001130700.2	ENSP00000356189.4
ENSG00000288520	ENST00000673182.1	c.1629+1304C>T		intron_variant	Intron 15 of 21			ENSP00000499846.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 65011 AN: 108190 Hom.: 14540 Cov.: 23

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.601

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.601 AC: 65066 AN: 108264 Hom.: 14554 Cov.: 23 AF XY: 0.597 AC XY: 31601 AN XY: 52946

African (AFR) AF: 0.605 AC: 17323 AN: 28632

American (AMR) AF: 0.684 AC: 8516 AN: 12442

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1109 AN: 1940

East Asian (EAS) AF: 0.101 AC: 291 AN: 2890

South Asian (SAS) AF: 0.494 AC: 1833 AN: 3710

European-Finnish (FIN) AF: 0.594 AC: 4441 AN: 7472

Middle Eastern (MID) AF: 0.577 AC: 113 AN: 196

European-Non Finnish (NFE) AF: 0.618 AC: 30220 AN: 48886

Other (OTH) AF: 0.599 AC: 896 AN: 1496

Alfa AF: 0.824 Hom.: 70867

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.11
DANN	Benign	0.14
PhyloP100		-0.39
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: rs1554817; hg19: chr6-154566421;