Variant 13-49691295-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032565.5(EBPL):c.130C>T(p.Leu44Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000983 in 1,383,148 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

EBPL
NM_032565.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

Variant links:

Genes affected

EBPL (HGNC:18061): (EBP like) Predicted to enable cholestenol delta-isomerase activity. Predicted to be involved in sterol metabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

EBPL links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EBPL	NM_032565.5 linkuse as main transcript	c.130C>T	p.Leu44Phe	missense_variant	1/4	ENST00000242827.11	NP_115954.1
EBPL	NM_001278636.1 linkuse as main transcript	c.130C>T	p.Leu44Phe	missense_variant	1/5		NP_001265565.1
EBPL	NR_103802.1 linkuse as main transcript	n.193C>T		non_coding_transcript_exon_variant	1/5
EBPL	NR_103803.1 linkuse as main transcript	n.193C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBPL	ENST00000242827.11 linkuse as main transcript	c.130C>T	p.Leu44Phe	missense_variant	1/4	1	NM_032565.5	ENSP00000242827	P1	Q9BY08-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152032

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000104

AC:

128

AN:

1231116

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

602756

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.0000606

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.00000919

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

Jul 12, 2023

The c.130C>T (p.L44F) alteration is located in exon 1 (coding exon 1) of the EBPL gene. This alteration results from a C to T substitution at nucleotide position 130, causing the leucine (L) at amino acid position 44 to be replaced by a phenylalanine (F). 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

0.24

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.28

.;.;T;.;.

Eigen

Benign

0.049

Eigen_PC

Benign

0.013

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.83

T;T;T;T;T

M_CAP

Pathogenic

0.60

MetaRNN

Uncertain

0.52

D;D;D;D;D

MetaSVM

Uncertain

0.75

MutationAssessor

Benign

0.89

.;L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.0

N;N;N;D;N

REVEL

Uncertain

0.51

Sift

Benign

0.39

T;D;T;D;T

Sift4G

Benign

0.36

T;D;T;D;D

Polyphen

1.0

.;.;D;.;D

Vest4

0.44

MutPred

0.60

Gain of catalytic residue at A43 (P = 0.0055);Gain of catalytic residue at A43 (P = 0.0055);Gain of catalytic residue at A43 (P = 0.0055);Gain of catalytic residue at A43 (P = 0.0055);Gain of catalytic residue at A43 (P = 0.0055);

MVP

0.57

MPC

0.73

ClinPred

0.87

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.16

gMVP

0.29

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