Genetic Variant LORICRIN:p.Cys51Cys (chr1-153261102-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000427.3(LORICRIN):c.153C>T(p.Cys51Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,423,500 control chromosomes in the GnomAD database, including 23,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1869 hom., cov: 28)

Exomes 𝑓: 0.17 ( 21192 hom. )

Consequence

LORICRIN
NM_000427.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.975

Variant links:

Genes affected

LORICRIN (HGNC:6663): (loricrin cornified envelope precursor protein) This gene encodes loricrin, a major protein component of the cornified cell envelope found in terminally differentiated epidermal cells. Mutations in this gene are associated with Vohwinkel's syndrome and progressive symmetric erythrokeratoderma, both inherited skin diseases. [provided by RefSeq, Jul 2008]

LORICRIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 1-153261102-C-T is Benign according to our data. Variant chr1-153261102-C-T is described in ClinVar as [Benign]. Clinvar id is 1266330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.975 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LORICRIN	NM_000427.3 link	c.153C>T	p.Cys51Cys	synonymous_variant	Exon 2 of 2	ENST00000368742.4	NP_000418.2	P23490

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LORICRIN	ENST00000368742.4 link	c.153C>T	p.Cys51Cys	synonymous_variant	Exon 2 of 2	1	NM_000427.3	ENSP00000357731.3		P23490

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20537

AN:

149666

Hom.:

1870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0405

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.292

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.291

AC:

15280

AN:

52420

Hom.:

2308

AF XY:

0.310

AC XY:

9523

AN XY:

30680

show subpopulations

Gnomad AFR exome

AF:

0.0704

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.331

Gnomad EAS exome

AF:

0.438

Gnomad SAS exome

AF:

0.464

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.247

Gnomad OTH exome

AF:

0.279

GnomAD4 exome

AF:

0.169

AC:

214908

AN:

1273732

Hom.:

21192

Cov.:

AF XY:

0.177

AC XY:

110308

AN XY:

624820

show subpopulations

Gnomad4 AFR exome

AF:

0.0388

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.259

Gnomad4 EAS exome

AF:

0.377

Gnomad4 SAS exome

AF:

0.385

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.137

AC:

20521

AN:

149768

Hom.:

1869

Cov.:

AF XY:

0.142

AC XY:

10394

AN XY:

73048

show subpopulations

Gnomad4 AFR

AF:

0.0404

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.253

Gnomad4 EAS

AF:

0.321

Gnomad4 SAS

AF:

0.377

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.145

Hom.:

297

Bravo

AF:

0.130

Asia WGS

AF:

0.306

AC:

1054

AN:

3458

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.5

DANN

Benign

0.74

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