Variant chr1-152511832-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_178438.5(LCE5A):c.298A>G(p.Ser100Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,613,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

LCE5A
NM_178438.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.626

Variant links:

Genes affected

LCE5A (HGNC:16614): (late cornified envelope 5A) Enables identical protein binding activity. Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

LCE5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0150793195).

BP6

Variant 1-152511832-A-G is Benign according to our data. Variant chr1-152511832-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2358081.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCE5A	NM_178438.5 linkuse as main transcript	c.298A>G	p.Ser100Gly	missense_variant	2/2	ENST00000334269.3	NP_848525.1	Q5TCM9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCE5A	ENST00000334269.3 linkuse as main transcript	c.298A>G	p.Ser100Gly	missense_variant	2/2	3	NM_178438.5	ENSP00000333952.2		Q5TCM9

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000850

AC:

AN:

246940

Hom.:

AF XY:

0.0000595

AC XY:

AN XY:

134542

show subpopulations

Gnomad AFR exome

AF:

0.0000685

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.0000359

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461502

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000112

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000746

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0080

DANN

Benign

0.42

DEOGEN2

Benign

0.016

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.19

M_CAP

Benign

0.0033

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.14

MutationTaster

Benign

1.0

PROVEAN

Benign

-1.4

REVEL

Benign

0.039

Sift

Benign

0.76

Sift4G

Benign

0.78

Polyphen

0.0

Vest4

0.088

MVP

0.014

MPC

0.15

ClinPred

0.017

GERP RS

-7.8

Varity_R

0.036

gMVP

0.028

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