rs2272381

Variant names:

• chr6-154221357-A-G
• rs2272381
• NM_001130700.2:c.321-29T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130700.2(IPCEF1):​c.321-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,583,206 control chromosomes in the GnomAD database, including 20,198 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.17 (2251 hom., cov: 33)
  • Exomes 𝑓: 0.16 (17947 hom.)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 10 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: This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPCEF1	NM_001130700.2	c.321-29T>C		intron_variant	Intron 6 of 11	ENST00000367220.9	NP_001124172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPCEF1	ENST00000367220.9	c.321-29T>C		intron_variant	Intron 6 of 11	2	NM_001130700.2	ENSP00000356189.4
ENSG00000288520	ENST00000673182.1	c.1704-29T>C		intron_variant	Intron 16 of 21			ENSP00000499846.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25840 AN: 152052 Hom.: 2251 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.164

GnomAD2 exomes AF: 0.158 AC: 39160 AN: 247458 AF XY: 0.162

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.189

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.155 AC: 222414 AN: 1431036 Hom.: 17947 Cov.: 25 AF XY: 0.158 AC XY: 112690 AN XY: 713662

African (AFR) AF: 0.220 AC: 7230 AN: 32844

American (AMR) AF: 0.115 AC: 5115 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4770 AN: 25924

East Asian (EAS) AF: 0.236 AC: 9321 AN: 39434

South Asian (SAS) AF: 0.208 AC: 17706 AN: 85144

European-Finnish (FIN) AF: 0.127 AC: 6756 AN: 53286

Middle Eastern (MID) AF: 0.168 AC: 960 AN: 5702

European-Non Finnish (NFE) AF: 0.148 AC: 161115 AN: 1084970

Other (OTH) AF: 0.159 AC: 9441 AN: 59390

GnomAD4 genome AF: 0.170 AC: 25851 AN: 152170 Hom.: 2251 Cov.: 33 AF XY: 0.169 AC XY: 12596 AN XY: 74388

African (AFR) AF: 0.218 AC: 9039 AN: 41502

American (AMR) AF: 0.122 AC: 1872 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3470

East Asian (EAS) AF: 0.202 AC: 1043 AN: 5176

South Asian (SAS) AF: 0.221 AC: 1067 AN: 4830

European-Finnish (FIN) AF: 0.133 AC: 1407 AN: 10588

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10308 AN: 68000

Other (OTH) AF: 0.162 AC: 343 AN: 2112

Alfa AF: 0.156 Hom.: 8370

Bravo AF: 0.169

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.9
DANN	Benign	0.83
PhyloP100		1.7
BranchPoint Hunter		4.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2272381; hg19: chr6-154542491; COSMIC: COSV54540345; COSMIC: COSV54540345;