rs2236256

Positions:

• chr6-154157305-C-A
• chr6-154157305-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.*2523G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,130 control chromosomes in the GnomAD database, including 20,822 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 0.52 (20795 hom., cov: 32)
  • Exomes 𝑓: 0.54 (27 hom.)
• Consequence: IPCEF1 NM_001130700.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702

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]

IPCEF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPCEF1	NM_001130700.2	c.*2523G>T		3_prime_UTR_variant	12/12	ENST00000367220.9	NP_001124172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPCEF1	ENST00000367220.9	c.*2523G>T		3_prime_UTR_variant	12/12	2	NM_001130700.2	ENSP00000356189.4

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78971 AN: 151854 Hom.: 20767 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.538 AC: 85 AN: 158 Hom.: 27 Cov.: 0 AF XY: 0.520 AC XY: 51 AN XY: 98

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.520 AC: 79045 AN: 151972 Hom.: 20795 Cov.: 32 AF XY: 0.515 AC XY: 38266 AN XY: 74272

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.525

Alfa AF: 0.540 Hom.: 28938

Bravo AF: 0.515

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.64

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: rs2236256; hg19: chr6-154478440;