Genetic Variant NM_000427.3:c.75_80dupTGGCGG (chr1-153261012-C-CGGCGGT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBA1

The NM_000427.3(LORICRIN):c.75_80dupTGGCGG(p.Gly26_Gly27dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,571,718 control chromosomes in the GnomAD database, including 35,515 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 4988 hom., cov: 24)

Exomes 𝑓: 0.20 ( 30527 hom. )

Consequence

LORICRIN
NM_000427.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.56

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 -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000427.3.

BP6

Variant 1-153261012-C-CGGCGGT is Benign according to our data. Variant chr1-153261012-C-CGGCGGT is described in ClinVar as [Benign]. Clinvar id is 2002883.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LORICRIN	NM_000427.3 link	c.75_80dupTGGCGG	p.Gly26_Gly27dup	disruptive_inframe_insertion	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.75_80dupTGGCGG	p.Gly26_Gly27dup	disruptive_inframe_insertion	Exon 2 of 2	1	NM_000427.3	ENSP00000357731.3		P23490

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36508

AN:

151280

Hom.:

4991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.369

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.0773

Gnomad SAS

AF:

0.0630

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.205

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.166

AC:

34460

AN:

207700

Hom.:

3500

AF XY:

0.163

AC XY:

18859

AN XY:

115594

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.0919

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.0779

Gnomad SAS exome

AF:

0.0603

Gnomad FIN exome

AF:

0.211

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.199

AC:

282161

AN:

1420324

Hom.:

30527

Cov.:

AF XY:

0.195

AC XY:

137356

AN XY:

706106

show subpopulations

Gnomad4 AFR exome

AF:

0.384

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.0616

Gnomad4 SAS exome

AF:

0.0629

Gnomad4 FIN exome

AF:

0.214

Gnomad4 NFE exome

AF:

0.212

Gnomad4 OTH exome

AF:

0.197

GnomAD4 genome

AF:

0.241

AC:

36530

AN:

151394

Hom.:

4988

Cov.:

AF XY:

0.236

AC XY:

17442

AN XY:

73978

show subpopulations

Gnomad4 AFR

AF:

0.375

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.0769

Gnomad4 SAS

AF:

0.0637

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.213

Asia WGS

AF:

0.0920

AC:

317

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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