6-154246542-G-A

Variant names:

• chr6-154246542-G-A
• rs7759388
• NM_001130700.2:c.246+49C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130700.2(IPCEF1):​c.246+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,560,458 control chromosomes in the GnomAD database, including 19,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (1603 hom., cov: 31)
  • Exomes 𝑓: 0.16 (18164 hom.)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.681
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 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.246+49C>T		intron	N/A	NP_001124172.1
	IPCEF1	NM_001130699.2		c.246+49C>T		intron	N/A	NP_001124171.1
	IPCEF1	NM_001394799.1		c.246+49C>T		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.246+49C>T		intron	N/A	ENSP00000356189.4
	ENSG00000288520	ENST00000673182.1		c.1629+49C>T		intron	N/A	ENSP00000499846.1
	IPCEF1	ENST00000422970.6	TSL:1	c.246+49C>T		intron	N/A	ENSP00000394751.2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20687 AN: 152014 Hom.: 1603 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.128 AC: 28384 AN: 221736 AF XY: 0.131

Gnomad AFR exome AF: 0.0990

Gnomad AMR exome AF: 0.0749

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.000844

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.155 AC: 218498 AN: 1408326 Hom.: 18164 Cov.: 29 AF XY: 0.154 AC XY: 107266 AN XY: 696968

African (AFR) AF: 0.0952 AC: 3052 AN: 32050

American (AMR) AF: 0.0795 AC: 3160 AN: 39728

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3541 AN: 22964

East Asian (EAS) AF: 0.000763 AC: 30 AN: 39310

South Asian (SAS) AF: 0.0711 AC: 5598 AN: 78738

European-Finnish (FIN) AF: 0.166 AC: 8563 AN: 51446

Middle Eastern (MID) AF: 0.155 AC: 855 AN: 5502

European-Non Finnish (NFE) AF: 0.172 AC: 185551 AN: 1080520

Other (OTH) AF: 0.140 AC: 8148 AN: 58068

GnomAD4 genome AF: 0.136 AC: 20688 AN: 152132 Hom.: 1603 Cov.: 31 AF XY: 0.132 AC XY: 9849 AN XY: 74370

African (AFR) AF: 0.102 AC: 4232 AN: 41502

American (AMR) AF: 0.102 AC: 1555 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3464

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0636 AC: 307 AN: 4824

European-Finnish (FIN) AF: 0.175 AC: 1855 AN: 10574

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.174 AC: 11804 AN: 67988

Other (OTH) AF: 0.136 AC: 287 AN: 2116

Alfa AF: 0.158 Hom.: 6480

Bravo AF: 0.129

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tramadol response Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.52
PhyloP100		-0.68
PromoterAI		-0.021	Neutral
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: rs7759388; hg19: chr6-154567676;