Variant chr1-152600988-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_178434.3(LCE3C):c.257G>A(p.Arg86His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 948,580 control chromosomes in the GnomAD database, including 777 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R86C) has been classified as Benign.

Frequency

Genomes: 𝑓 0.014 ( 386 hom., cov: 16)

Exomes 𝑓: 0.0015 ( 391 hom. )

Consequence

LCE3C
NM_178434.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.887

Variant links:

Genes affected

LCE3C (HGNC:16612): (late cornified envelope 3C) Involved in defense response to Gram-negative bacterium; defense response to Gram-positive bacterium; and killing of cells of other organism. [provided by Alliance of Genome Resources, Apr 2022]

LCE3C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002729535).

BP6

Variant 1-152600988-G-A is Benign according to our data. Variant chr1-152600988-G-A is described in ClinVar as [Benign]. Clinvar id is 775600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (1317/95786) while in subpopulation AFR AF= 0.0394 (1282/32534). AF 95% confidence interval is 0.0376. There are 386 homozygotes in gnomad4. There are 634 alleles in male gnomad4 subpopulation. Median coverage is 16. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 386 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCE3C	NM_178434.3 linkuse as main transcript	c.257G>A	p.Arg86His	missense_variant	2/2	ENST00000684028.1	NP_848521.1	Q5T5A8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCE3C	ENST00000684028.1 linkuse as main transcript	c.257G>A	p.Arg86His	missense_variant	2/2		NM_178434.3	ENSP00000507204.1		Q5T5A8
LCE3C	ENST00000333881.3 linkuse as main transcript	c.257G>A	p.Arg86His	missense_variant	1/1	6		ENSP00000334644.3		Q5T5A8

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

1311

AN:

95684

Hom.:

384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00304

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000775

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00459

GnomAD3 exomes

AF:

0.00373

AC:

557

AN:

149394

Hom.:

167

AF XY:

0.00322

AC XY:

259

AN XY:

80536

show subpopulations

Gnomad AFR exome

AF:

0.0392

Gnomad AMR exome

AF:

0.00132

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000357

Gnomad SAS exome

AF:

0.000946

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.00151

AC:

1289

AN:

852794

Hom.:

391

Cov.:

AF XY:

0.00129

AC XY:

548

AN XY:

423774

show subpopulations

Gnomad4 AFR exome

AF:

0.0404

Gnomad4 AMR exome

AF:

0.00149

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000396

Gnomad4 SAS exome

AF:

0.000865

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000943

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.0137

AC:

1317

AN:

95786

Hom.:

386

Cov.:

AF XY:

0.0137

AC XY:

634

AN XY:

46136

show subpopulations

Gnomad4 AFR

AF:

0.0394

Gnomad4 AMR

AF:

0.00303

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000776

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00455

Alfa

AF:

0.00711

Hom.:

ESP6500AA

AF:

0.0355

AC:

128

ESP6500EA

AF:

0.000375

AC:

ExAC

AF:

0.00456

AC:

364

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.0036

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.050

REVEL

Benign

0.021

Sift

Benign

0.19

Sift4G

Benign

0.52

Polyphen

0.030

Vest4

0.24

MVP

0.17

MPC

0.92

ClinPred

0.0087

GERP RS

3.1

Varity_R

0.022

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