chr6-154157305-C-A

Variant names:

• chr6-154157305-C-A
• rs2236256
• NM_001130700.2:c.*2523G>T

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 26 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]

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: 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130700.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPCEF1	NM_001130700.2	MANE Select	c.*2523G>T		3_prime_UTR	Exon 12 of 12	NP_001124172.1	Q8WWN9-2
	IPCEF1	NM_001130699.2		c.*2523G>T		3_prime_UTR	Exon 13 of 13	NP_001124171.1	Q8WWN9-2
	IPCEF1	NM_001394799.1		c.*2523G>T		3_prime_UTR	Exon 13 of 13	NP_001381728.1	Q8WWN9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPCEF1	ENST00000367220.9	TSL:2 MANE Select	c.*2523G>T		3_prime_UTR	Exon 12 of 12	ENSP00000356189.4	Q8WWN9-2
	IPCEF1	ENST00000265198.8	TSL:1	c.*2523G>T		3_prime_UTR	Exon 12 of 12	ENSP00000265198.4	Q8WWN9-1
	OPRM1	ENST00000337049.8	TSL:1	c.1164+65833C>A		intron	N/A	ENSP00000338381.4	P35372-5

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

African (AFR) AF: 1.00 AC: 6 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.313 AC: 5 AN: 16

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.542 AC: 65 AN: 120

Other (OTH) AF: 1.00 AC: 6 AN: 6

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

African (AFR) AF: 0.514 AC: 21275 AN: 41418

American (AMR) AF: 0.408 AC: 6227 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2473 AN: 3470

East Asian (EAS) AF: 0.487 AC: 2518 AN: 5170

South Asian (SAS) AF: 0.428 AC: 2062 AN: 4814

European-Finnish (FIN) AF: 0.530 AC: 5596 AN: 10560

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37157 AN: 67958

Other (OTH) AF: 0.525 AC: 1107 AN: 2110

Alfa AF: 0.537 Hom.: 69724

Bravo AF: 0.515

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.64
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236256; hg19: chr6-154478440;