Variant chr1-152805162-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_178351.4(LCE1C):c.317G>A(p.Cys106Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,612,220 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 22 hom., cov: 31)

Exomes 𝑓: 0.00070 ( 9 hom. )

Consequence

LCE1C
NM_178351.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.47

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005890101).

BP6

Variant 1-152805162-C-T is Benign according to our data. Variant chr1-152805162-C-T is described in ClinVar as [Benign]. Clinvar id is 787217.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00709 (1079/152280) while in subpopulation AFR AF= 0.0248 (1032/41568). AF 95% confidence interval is 0.0236. There are 22 homozygotes in gnomad4. There are 479 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCE1C	NM_178351.4 linkuse as main transcript	c.317G>A	p.Cys106Tyr	missense_variant	2/2	ENST00000607093.2
LCE1C	NM_001276331.2 linkuse as main transcript	c.227G>A	p.Cys76Tyr	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCE1C	ENST00000607093.2 linkuse as main transcript	c.317G>A	p.Cys106Tyr	missense_variant	2/2		NM_178351.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00708

AC:

1078

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

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:

0.00

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00173

AC:

430

AN:

247872

Hom.:

AF XY:

0.00130

AC XY:

175

AN XY:

134612

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000701

AC:

1024

AN:

1459940

Hom.:

Cov.:

AF XY:

0.000609

AC XY:

442

AN XY:

726118

show subpopulations

Gnomad4 AFR exome

AF:

0.0246

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000198

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.00709

AC:

1079

AN:

152280

Hom.:

Cov.:

AF XY:

0.00643

AC XY:

479

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0248

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00809

ESP6500AA

AF:

0.0224

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.00220

AC:

267

Asia WGS

AF:

0.00144

AC:

AN:

3478

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

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.044

Eigen

Uncertain

0.38

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0059

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.99

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.55

MVP

0.22

ClinPred

0.042

GERP RS

2.9

Varity_R

0.73

gMVP

0.040

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