Variant chr1-152805279-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_178351.4(LCE1C):c.200G>T(p.Cys67Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000786 in 1,614,070 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00045 ( 10 hom. )

Consequence

LCE1C
NM_178351.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

LCE1C (HGNC:29464): (late cornified envelope 1C) Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

LCE1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008681148).

BP6

Variant 1-152805279-C-A is Benign according to our data. Variant chr1-152805279-C-A is described in ClinVar as [Benign]. Clinvar id is 775142.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCE1C	NM_178351.4 linkuse as main transcript	c.200G>T	p.Cys67Phe	missense_variant	2/2	ENST00000607093.2
LCE1C	NM_001276331.2 linkuse as main transcript	c.110G>T	p.Cys37Phe	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCE1C	ENST00000607093.2 linkuse as main transcript	c.200G>T	p.Cys67Phe	missense_variant	2/2		NM_178351.4	P1
LCE1C	ENST00000606576.1 linkuse as main transcript	c.110G>T	p.Cys37Phe	missense_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.00400

AC:

609

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00102

AC:

257

AN:

250804

Hom.:

AF XY:

0.000737

AC XY:

100

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000452

AC:

660

AN:

1461764

Hom.:

Cov.:

AF XY:

0.000378

AC XY:

275

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0156

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.000944

GnomAD4 genome

AF:

0.00400

AC:

609

AN:

152306

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

286

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.00447

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00123

AC:

149

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.048

T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.38

T;.

MetaRNN

Benign

0.0087

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.63

Sift4G

Pathogenic

0.0010

D;.

Polyphen

1.0

D;.

Vest4

0.53

MVP

0.36

ClinPred

0.035

GERP RS

3.9

Varity_R

0.90

gMVP

0.028

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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