Variant 1-152776583-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_178354.3(LCE1F):c.212G>A(p.Gly71Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,459,412 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G71R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LCE1F
NM_178354.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

LCE1F (HGNC:29467): (late cornified envelope 1F) Enables identical protein binding activity. Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

LCE1F links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000132 (193/1459412) while in subpopulation MID AF= 0.0191 (90/4722). AF 95% confidence interval is 0.0159. There are 0 homozygotes in gnomad4_exome. There are 98 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCE1F	NM_178354.3 linkuse as main transcript	c.212G>A	p.Gly71Glu	missense_variant	2/2	ENST00000334371.4	NP_848131.1	Q5T754

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCE1F	ENST00000334371.4 linkuse as main transcript	c.212G>A	p.Gly71Glu	missense_variant	2/2	6	NM_178354.3	ENSP00000334187.2		Q5T754

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150534

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000245

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:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000360

AC:

AN:

249838

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.0000635

Gnomad AMR exome

AF:

0.00

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:

0.0000709

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

193

AN:

1459412

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

726000

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000378

Gnomad4 NFE exome

AF:

0.0000657

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000199

AC:

AN:

150650

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73650

show subpopulations

Gnomad4 AFR

AF:

0.0000245

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:

0.0000296

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

ExAC

AF:

0.0000412

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

Aug 08, 2023

The c.212G>A (p.G71E) alteration is located in exon 1 (coding exon 1) of the LCE1F gene. This alteration results from a G to A substitution at nucleotide position 212, causing the glycine (G) at amino acid position 71 to be replaced by a glutamic acid (E). 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

0.38

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.38

M_CAP

Benign

0.0027

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.12

Sift4G

Uncertain

0.042

Polyphen

1.0

Vest4

0.57

MVP

0.35

MPC

0.067

ClinPred

0.19

GERP RS

4.3

Varity_R

0.77

gMVP

0.020

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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