rs6935927

Positions:

• chr6-154239203-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPCEF1	NM_001130700.2	c.246+7388A>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.246+7388A>G		intron_variant		2	NM_001130700.2	ENSP00000356189	A2

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

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.0576

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.422

Alfa AF: 0.435 Hom.: 29901

Bravo AF: 0.433

Asia WGS AF: 0.255 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.71

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: rs6935927; hg19: chr6-154560337;