rs6935927

Variant names:

• chr6-154239203-T-C
• rs6935927
• NM_001130700.2:c.246+7388A>G

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+7388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,980 control chromosomes in the GnomAD database, including 14,554 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 0.43 (14554 hom., cov: 32)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.551 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+7388A>G		intron	N/A	NP_001124172.1
	IPCEF1	NM_001130699.2		c.246+7388A>G		intron	N/A	NP_001124171.1
	IPCEF1	NM_001394799.1		c.246+7388A>G		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+7388A>G		intron	N/A	ENSP00000356189.4
	ENSG00000288520	ENST00000673182.1		c.1629+7388A>G		intron	N/A	ENSP00000499846.1
	IPCEF1	ENST00000422970.6	TSL:1	c.246+7388A>G		intron	N/A	ENSP00000394751.2

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65033 AN: 151864 Hom.: 14544 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.428 AC: 65079 AN: 151980 Hom.: 14554 Cov.: 32 AF XY: 0.426 AC XY: 31645 AN XY: 74302

African (AFR) AF: 0.409 AC: 16960 AN: 41430

American (AMR) AF: 0.561 AC: 8576 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3472

East Asian (EAS) AF: 0.0576 AC: 298 AN: 5176

South Asian (SAS) AF: 0.388 AC: 1868 AN: 4818

European-Finnish (FIN) AF: 0.429 AC: 4527 AN: 10554

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30403 AN: 67938

Other (OTH) AF: 0.422 AC: 891 AN: 2110

Alfa AF: 0.435 Hom.: 61861

Bravo AF: 0.433

Asia WGS AF: 0.255 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.71
PhyloP100		0.18
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: rs6935927; hg19: chr6-154560337;