6-154166286-C-T

Position:

• chr6-154166286-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001130700.2(IPCEF1):​c.1104+1634G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,146 control chromosomes in the GnomAD database, including 2,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2896 hom., cov: 33)
• Consequence: IPCEF1 NM_001130700.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.251

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-154166286-C-T is Benign according to our data. Variant chr6-154166286-C-T is described in ClinVar as [Benign]. Clinvar id is 1277133.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPCEF1	NM_001130700.2	c.1104+1634G>A		intron_variant		ENST00000367220.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPCEF1	ENST00000367220.9	c.1104+1634G>A		intron_variant		2	NM_001130700.2	A2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27382 AN: 152028 Hom.: 2882 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.180 AC: 27441 AN: 152146 Hom.: 2896 Cov.: 33 AF XY: 0.182 AC XY: 13509 AN XY: 74376

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.196

Alfa AF: 0.141 Hom.: 2341

Bravo AF: 0.182

Asia WGS AF: 0.328 AC: 1141 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.37

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: rs2281617; hg19: chr6-154487421;