6-154212799-G-C

Position:

chr6-154212799-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130700.2(IPCEF1):c.508C>G(p.Pro170Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P170L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

IPCEF1
NM_001130700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.49

Variant links:

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]

IPCEF1 links:

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]

OPRM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2049309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPCEF1	NM_001130700.2 linkuse as main transcript	c.508C>G	p.Pro170Ala	missense_variant	9/12	ENST00000367220.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPCEF1	ENST00000367220.9 linkuse as main transcript	c.508C>G	p.Pro170Ala	missense_variant	9/12	2	NM_001130700.2	A2	Q8WWN9-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251276

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461256

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 04, 2024

The c.508C>G (p.P170A) alteration is located in exon 10 (coding exon 7) of the IPCEF1 gene. This alteration results from a C to G substitution at nucleotide position 508, causing the proline (P) at amino acid position 170 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.094

T;.;.;.;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.63

T;.;T;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.20

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.;.;.;.

MutationTaster

Benign

0.54

N;N;N;N;D

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-6.2

D;D;D;D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0080

D;D;D;D;D

Sift4G

Benign

0.062

T;T;T;T;.

Polyphen

0.67

P;D;D;.;.

Vest4

0.29

MutPred

0.28

Loss of glycosylation at P169 (P = 0.0055);.;.;.;.;

MVP

0.29

MPC

0.31

ClinPred

0.31

GERP RS

5.1

Varity_R

0.20

gMVP

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over