Genetic Variant IPCEF1:c.246+49C>T (chr6-154246542-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.681

Variant links:

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]

IPCEF1 links:

ENSG00000288520 (HGNC:):

ENSG00000288520 links:

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]

OPRM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPCEF1	NM_001130700.2 link	c.246+49C>T		intron_variant	Intron 5 of 11	ENST00000367220.9	NP_001124172.1	Q8WWN9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPCEF1	ENST00000367220.9 link	c.246+49C>T		intron_variant	Intron 5 of 11	2	NM_001130700.2	ENSP00000356189.4		Q8WWN9-2
ENSG00000288520	ENST00000673182.1 link	c.1629+49C>T		intron_variant	Intron 15 of 21			ENSP00000499846.1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20687

AN:

152014

Hom.:

1603

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.128

AC:

28384

AN:

221736

Hom.:

2307

AF XY:

0.131

AC XY:

15554

AN XY:

118716

show subpopulations

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 SAS exome

AF:

0.0724

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.:

AF XY:

0.154

AC XY:

107266

AN XY:

696968

show subpopulations

Gnomad4 AFR exome

AF:

0.0952

Gnomad4 AMR exome

AF:

0.0795

Gnomad4 ASJ exome

AF:

0.154

Gnomad4 EAS exome

AF:

0.000763

Gnomad4 SAS exome

AF:

0.0711

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.136

AC:

20688

AN:

152132

Hom.:

1603

Cov.:

AF XY:

0.132

AC XY:

9849

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0636

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.163

Hom.:

4349

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

LINK: link

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.2

DANN

Benign

0.52

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over