Genetic Variant LORICRIN:p.Gly24_Gly27dup (chr1-153261012-C-CGGCGGTGGCGGT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_000427.3(LORICRIN):c.69_80dupTGGCGGTGGCGG(p.Gly24_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 0.000156 in 1,572,620 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 1 hom., cov: 24)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

LORICRIN
NM_000427.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely 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 Likely_benign. Variant got -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000427.3.

BP6

Variant 1-153261012-C-CGGCGGTGGCGGT is Benign according to our data. Variant chr1-153261012-C-CGGCGGTGGCGGT is described in ClinVar as [Likely_benign]. Clinvar id is 2081646.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LORICRIN	NM_000427.3 link	c.69_80dupTGGCGGTGGCGG	p.Gly24_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.69_80dupTGGCGGTGGCGG	p.Gly24_Gly27dup	disruptive_inframe_insertion	Exon 2 of 2	1	NM_000427.3	ENSP00000357731.3		P23490

Frequencies

GnomAD3 genomes

AF:

0.000680

AC:

103

AN:

151414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.000118

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000159

AC:

AN:

207700

Hom.:

AF XY:

0.000190

AC XY:

AN XY:

115594

show subpopulations

Gnomad AFR exome

AF:

0.00180

Gnomad AMR exome

AF:

0.000100

Gnomad ASJ exome

AF:

0.000224

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000722

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000876

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000999

AC:

142

AN:

1421092

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

706506

show subpopulations

Gnomad4 AFR exome

AF:

0.00225

Gnomad4 AMR exome

AF:

0.0000728

Gnomad4 ASJ exome

AF:

0.000239

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000728

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000431

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.000680

AC:

103

AN:

151528

Hom.:

Cov.:

AF XY:

0.000635

AC XY:

AN XY:

74038

show subpopulations

Gnomad4 AFR

AF:

0.00216

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00143

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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