Variant 1-186406208-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017847.6(ODR4):c.1126G>A(p.Glu376Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000601 in 1,611,400 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 1 hom. )

Consequence

ODR4
NM_017847.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.74

Variant links:

Genes affected

ODR4 (HGNC:24299): (odr-4 GPCR localization factor homolog) Predicted to be involved in protein localization. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ODR4 links:

ODR4 (HGNC:):

ODR4 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=0.20984805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODR4	NM_017847.6 linkuse as main transcript	c.1126G>A	p.Glu376Lys	missense_variant	12/14	ENST00000287859.11	NP_060317.3	Q5SWX8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ODR4	ENST00000287859.11 linkuse as main transcript	c.1126G>A	p.Glu376Lys	missense_variant	12/14	1	NM_017847.6	ENSP00000287859.6	Q5SWX8-1
ODR4	ENST00000367470.8 linkuse as main transcript	c.1057G>A	p.Glu353Lys	missense_variant	11/13	5		ENSP00000356440.3	Q5SWX8-2
ODR4	ENST00000419367.8 linkuse as main transcript	c.1030G>A	p.Glu344Lys	missense_variant	11/13	2		ENSP00000395084.3	Q5SWX8-4
ODR4	ENST00000478571.1 linkuse as main transcript	n.239G>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000587

AC:

145

AN:

246878

Hom.:

AF XY:

0.000612

AC XY:

AN XY:

133974

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.000238

Gnomad ASJ exome

AF:

0.00309

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000872

Gnomad OTH exome

AF:

0.000673

GnomAD4 exome

AF:

0.000603

AC:

880

AN:

1459130

Hom.:

Cov.:

AF XY:

0.000599

AC XY:

435

AN XY:

725844

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.000225

Gnomad4 ASJ exome

AF:

0.00276

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000681

Gnomad4 OTH exome

AF:

0.000597

GnomAD4 genome

AF:

0.000578

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000911

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000977

Hom.:

Bravo

AF:

0.000646

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000270

AC:

ESP6500EA

AF:

0.000731

AC:

ExAC

AF:

0.000604

AC:

EpiCase

AF:

0.00121

EpiControl

AF:

0.00131

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 11, 2021

The c.1126G>A (p.E376K) alteration is located in exon 12 (coding exon 11) of the C1orf27 gene. This alteration results from a G to A substitution at nucleotide position 1126, causing the glutamic acid (E) at amino acid position 376 to be replaced by a lysine (K). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

.;.;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.7

.;.;M

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.91

MVP

0.48

MPC

0.62

ClinPred

0.11

GERP RS

5.4

Varity_R

0.72

gMVP

0.71

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