rs9371781

Positions:

• chr6-154231073-A-C

Variant summary

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

The NM_001130700.2(IPCEF1):​c.247-7830T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,008 control chromosomes in the GnomAD database, including 9,267 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 0.34 (9267 hom., cov: 32)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02

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]

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPCEF1	NM_001130700.2	c.247-7830T>G		intron_variant		ENST00000367220.9	NP_001124172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPCEF1	ENST00000367220.9	c.247-7830T>G		intron_variant		2	NM_001130700.2	ENSP00000356189	A2

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51567 AN: 151890 Hom.: 9248 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0842

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.340 AC: 51628 AN: 152008 Hom.: 9267 Cov.: 32 AF XY: 0.339 AC XY: 25206 AN XY: 74312

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.0844

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.332

Alfa AF: 0.324 Hom.: 4525

Bravo AF: 0.353

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.37

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: rs9371781; hg19: chr6-154552207;