chr6-154161032-C-T

Position:

• chr6-154161032-C-T

Variant summary

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

The NM_001130700.2(IPCEF1):​c.1105-992G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,930 control chromosomes in the GnomAD database, including 34,688 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 0.67 (34688 hom., cov: 30)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPCEF1	NM_001130700.2	c.1105-992G>A		intron_variant		ENST00000367220.9	NP_001124172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPCEF1	ENST00000367220.9	c.1105-992G>A		intron_variant		2	NM_001130700.2	ENSP00000356189.4
ENSG00000288520	ENST00000673182.1	c.2488-992G>A		intron_variant				ENSP00000499846.1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101630 AN: 151812 Hom.: 34649 Cov.: 30

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.669 AC: 101715 AN: 151930 Hom.: 34688 Cov.: 30 AF XY: 0.668 AC XY: 49634 AN XY: 74266

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.678

Alfa AF: 0.638 Hom.: 23160

Bravo AF: 0.666

Asia WGS AF: 0.768 AC: 2671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.099
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs1918760; hg19: chr6-154482167;