rs2272381

chr6-154221357-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130700.2(IPCEF1):c.321-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,583,206 control chromosomes in the GnomAD database, including 20,198 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 0.17 (2251 hom., cov: 33)
  • Exomes 𝑓: 0.16 (17947 hom.)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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]

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPCEF1	NM_001130700.2	c.321-29T>C		intron_variant		ENST00000367220.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPCEF1	ENST00000367220.9	c.321-29T>C		intron_variant		2	NM_001130700.2	A2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25840 AN: 152052 Hom.: 2251 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.164

GnomAD3 exomes AF: 0.158 AC: 39160 AN: 247458 Hom.: 3261 AF XY: 0.162 AC XY: 21656 AN XY: 133692

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.189

Gnomad SAS exome AF: 0.213

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.155 AC: 222414 AN: 1431036 Hom.: 17947 Cov.: 25 AF XY: 0.158 AC XY: 112690 AN XY: 713662

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.170 AC: 25851 AN: 152170 Hom.: 2251 Cov.: 33 AF XY: 0.169 AC XY: 12596 AN XY: 74388

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.162

Alfa AF: 0.154 Hom.: 3865

Bravo AF: 0.169

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.9
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2272381; hg19: chr6-154542491; COSMIC: COSV54540345; COSMIC: COSV54540345;