Genetic Variant LCE1D:p.Ter115Glyext*? (chr1-152798137-T-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM4BA1

The NM_178352.3(LCE1D):c.343T>G(p.Ter115Glyext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 1,374,926 control chromosomes in the GnomAD database, including 4,991 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.057 ( 341 hom., cov: 22)

Exomes 𝑓: 0.050 ( 4650 hom. )

Consequence

LCE1D
NM_178352.3 stop_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.830

Publications

7 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: Likely_benign. The variant received -6 ACMG points.

PM4

Stoplost variant in NM_178352.3 Downstream stopcodon found after 138 codons.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE1D	NM_178352.3 link	c.343T>G	p.Ter115Glyext*?	stop_lost	Exon 2 of 2	ENST00000326233.7	NP_848129.1	Q5T752

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCE1D	ENST00000326233.7 link	c.343T>G	p.Ter115Glyext*?	stop_lost	Exon 2 of 2	5	NM_178352.3	ENSP00000316737.6		Q5T752

Frequencies

GnomAD3 genomes

AF:

0.0566

AC:

7678

AN:

135574

Hom.:

340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0875

Gnomad AMI

AF:

0.0687

Gnomad AMR

AF:

0.0455

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.0384

Gnomad SAS

AF:

0.0798

Gnomad FIN

AF:

0.0416

Gnomad MID

AF:

0.0438

Gnomad NFE

AF:

0.0424

Gnomad OTH

AF:

0.0538

GnomAD2 exomes

AF:

0.0509

AC:

9126

AN:

179442

AF XY:

0.0529

show subpopulations

Gnomad AFR exome

AF:

0.0891

Gnomad AMR exome

AF:

0.0273

Gnomad ASJ exome

AF:

0.0520

Gnomad EAS exome

AF:

0.0360

Gnomad FIN exome

AF:

0.0439

Gnomad NFE exome

AF:

0.0444

Gnomad OTH exome

AF:

0.0546

GnomAD4 exome

AF:

0.0497

AC:

61638

AN:

1239246

Hom.:

4650

Cov.:

AF XY:

0.0510

AC XY:

31227

AN XY:

611998

show subpopulations

African (AFR)

AF:

0.0934

AC:

2757

AN:

29524

American (AMR)

AF:

0.0288

AC:

968

AN:

33616

Ashkenazi Jewish (ASJ)

AF:

0.0482

AC:

951

AN:

19716

East Asian (EAS)

AF:

0.0331

AC:

1297

AN:

39144

South Asian (SAS)

AF:

0.0912

AC:

6700

AN:

73466

European-Finnish (FIN)

AF:

0.0461

AC:

2126

AN:

46120

Middle Eastern (MID)

AF:

0.0596

AC:

222

AN:

3726

European-Non Finnish (NFE)

AF:

0.0462

AC:

43522

AN:

942222

Other (OTH)

AF:

0.0599

AC:

3095

AN:

51712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

1609

3218

4827

6436

8045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1726

3452

5178

6904

8630

<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

AF:

0.0567

AC:

7688

AN:

135680

Hom.:

341

Cov.:

AF XY:

0.0566

AC XY:

3764

AN XY:

66464

show subpopulations

African (AFR)

AF:

0.0875

AC:

3326

AN:

37992

American (AMR)

AF:

0.0454

AC:

628

AN:

13828

Ashkenazi Jewish (ASJ)

AF:

0.0429

AC:

135

AN:

3148

East Asian (EAS)

AF:

0.0383

AC:

197

AN:

5140

South Asian (SAS)

AF:

0.0792

AC:

346

AN:

4368

European-Finnish (FIN)

AF:

0.0416

AC:

390

AN:

9368

Middle Eastern (MID)

AF:

0.0388

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0424

AC:

2500

AN:

58928

Other (OTH)

AF:

0.0543

AC:

AN:

1806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

259

518

777

1036

1295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0374

Hom.:

TwinsUK

AF:

0.0413

AC:

153

ALSPAC

AF:

0.0431

AC:

166

ESP6500AA

AF:

0.0673

AC:

271

ESP6500EA

AF:

0.0356

AC:

266

ExAC

AF:

0.0443

AC:

5023

Asia WGS

AF:

0.0680

AC:

238

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.9

(source)

DANN

Benign

0.56

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.36

PhyloP100

0.83

Vest4

0.0070

GERP RS

2.4

Mutation Taster

=195/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over