NM_001130700.2:c.537+4390G>A

Variant names:

• chr6-154208380-C-T
• rs9479791
• NM_001130700.2:c.537+4390G>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.537+4390G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,146 control chromosomes in the GnomAD database, including 2,232 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 0.16 (2232 hom., cov: 32)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPCEF1	NM_001130700.2	c.537+4390G>A		intron_variant	Intron 9 of 11	ENST00000367220.9	NP_001124172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPCEF1	ENST00000367220.9	c.537+4390G>A		intron_variant	Intron 9 of 11	2	NM_001130700.2	ENSP00000356189.4
ENSG00000288520	ENST00000673182.1	c.1920+4390G>A		intron_variant	Intron 19 of 21			ENSP00000499846.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24251 AN: 152028 Hom.: 2230 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.159 AC: 24267 AN: 152146 Hom.: 2232 Cov.: 32 AF XY: 0.161 AC XY: 11954 AN XY: 74392

African (AFR) AF: 0.246 AC: 10222 AN: 41472

American (AMR) AF: 0.0927 AC: 1418 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3470

East Asian (EAS) AF: 0.202 AC: 1041 AN: 5164

South Asian (SAS) AF: 0.205 AC: 987 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1712 AN: 10594

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8269 AN: 68000

Other (OTH) AF: 0.145 AC: 306 AN: 2112

Alfa AF: 0.138 Hom.: 1141

Bravo AF: 0.156

Asia WGS AF: 0.202 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.77
PhyloP100		-1.5
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: rs9479791; hg19: chr6-154529514;