6-154247041-G-C

Variant names:

• chr6-154247041-G-C
• rs9322453
• NM_001130700.2:c.77-281C>G

Variant summary

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

The NM_001130700.2(IPCEF1):​c.77-281C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 409,484 control chromosomes in the GnomAD database, including 30,483 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 0.36 (10478 hom., cov: 31)
  • Exomes 𝑓: 0.38 (20005 hom.)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 4 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: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPCEF1	NM_001130700.2	c.77-281C>G		intron_variant	Intron 4 of 11	ENST00000367220.9	NP_001124172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPCEF1	ENST00000367220.9	c.77-281C>G		intron_variant	Intron 4 of 11	2	NM_001130700.2	ENSP00000356189.4
ENSG00000288520	ENST00000673182.1	c.1460-281C>G		intron_variant	Intron 14 of 21			ENSP00000499846.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55244 AN: 151544 Hom.: 10481 Cov.: 31

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.383 AC: 98847 AN: 257838 Hom.: 20005 Cov.: 4 AF XY: 0.381 AC XY: 50377 AN XY: 132136

African (AFR) AF: 0.291 AC: 2439 AN: 8370

American (AMR) AF: 0.259 AC: 2611 AN: 10084

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 4749 AN: 8984

East Asian (EAS) AF: 0.249 AC: 5312 AN: 21328

South Asian (SAS) AF: 0.214 AC: 2753 AN: 12856

European-Finnish (FIN) AF: 0.416 AC: 7025 AN: 16878

Middle Eastern (MID) AF: 0.426 AC: 509 AN: 1194

European-Non Finnish (NFE) AF: 0.415 AC: 67066 AN: 161762

Other (OTH) AF: 0.390 AC: 6383 AN: 16382

GnomAD4 genome AF: 0.364 AC: 55250 AN: 151646 Hom.: 10478 Cov.: 31 AF XY: 0.361 AC XY: 26728 AN XY: 74084

African (AFR) AF: 0.295 AC: 12177 AN: 41320

American (AMR) AF: 0.298 AC: 4534 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1918 AN: 3468

East Asian (EAS) AF: 0.277 AC: 1434 AN: 5170

South Asian (SAS) AF: 0.227 AC: 1090 AN: 4812

European-Finnish (FIN) AF: 0.417 AC: 4354 AN: 10430

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28425 AN: 67914

Other (OTH) AF: 0.380 AC: 798 AN: 2100

Alfa AF: 0.383 Hom.: 1474

Bravo AF: 0.359

Asia WGS AF: 0.242 AC: 843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		1.0
PromoterAI		0.088	Neutral
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: rs9322453; hg19: chr6-154568175; COSMIC: COSV54550625; COSMIC: COSV54550625;