Genetic Variant LCE1D:p.Arg83Cys (chr1-152798041-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_178352.3(LCE1D):c.247C>T(p.Arg83Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,304,222 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000037 ( 2 hom., cov: 22)

Exomes 𝑓: 0.000015 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

LCE1D
NM_178352.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.153

Publications

2 publications found

Variant links:

Genes affected

LCE1D (HGNC:29465): (late cornified envelope 1D) Enables identical protein binding activity. Involved in cognition. Acts upstream of or within cellular response to calcium ion. Located in cornified envelope and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LCE1D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06822631).

BP6

Variant 1-152798041-C-T is Benign according to our data. Variant chr1-152798041-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3118037.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178352.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE1D	NM_178352.3	MANE Select	c.247C>T	p.Arg83Cys	missense	Exon 2 of 2	NP_848129.1	Q5T752

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE1D	ENST00000326233.7	TSL:5 MANE Select	c.247C>T	p.Arg83Cys	missense	Exon 2 of 2	ENSP00000316737.6	Q5T752

Frequencies

GnomAD3 genomes

AF:

0.0000371

AC:

AN:

134600

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000856

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000309

AC:

AN:

226876

AF XY:

0.0000405

show subpopulations

Gnomad AFR exome

AF:

0.000140

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000309

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1304222

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

649672

show subpopulations

African (AFR)

AF:

0.0000314

AC:

AN:

31814

American (AMR)

AF:

0.00

AC:

AN:

43016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23950

East Asian (EAS)

AF:

0.00

AC:

AN:

39622

South Asian (SAS)

AF:

0.0000483

AC:

AN:

82884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4042

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

975446

Other (OTH)

AF:

0.00

AC:

AN:

54724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000371

AC:

AN:

134600

Hom.:

Cov.:

AF XY:

0.0000456

AC XY:

AN XY:

65740

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37756

American (AMR)

AF:

0.00

AC:

AN:

13726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3134

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0000856

AC:

AN:

58380

Other (OTH)

AF:

0.00

AC:

AN:

1772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000267

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.17

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.46

M_CAP

Benign

0.0052

MetaRNN

Benign

0.068

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

PhyloP100

-0.15

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.053

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.17

MutPred

0.17

Loss of MoRF binding (P = 0.0274)

MVP

0.20

MPC

0.40

ClinPred

0.024

GERP RS

-2.0

Varity_R

0.57

gMVP

0.035

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over