Variant 1-153261059-T-TCGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PM4_SupportingBP6BS1BS2

The NM_000427.3(LORICRIN):c.121_123dupGGC(p.Gly41dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 1,513,536 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0035 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0044 ( 18 hom. )

Consequence

LORICRIN
NM_000427.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.0520

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. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 1-153261059-T-TCGG is Benign according to our data. Variant chr1-153261059-T-TCGG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 587580.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00351 (500/142352) while in subpopulation NFE AF= 0.00572 (368/64352). AF 95% confidence interval is 0.00524. There are 0 homozygotes in gnomad4. There are 236 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 500 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LORICRIN	NM_000427.3 linkuse as main transcript	c.121_123dupGGC	p.Gly41dup	conservative_inframe_insertion	2/2	ENST00000368742.4	NP_000418.2	P23490

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LORICRIN	ENST00000368742.4 linkuse as main transcript	c.121_123dupGGC	p.Gly41dup	conservative_inframe_insertion	2/2	1	NM_000427.3	ENSP00000357731.3		P23490

Frequencies

GnomAD3 genomes

AF:

0.00352

AC:

500

AN:

142234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00472

Gnomad AMR

AF:

0.000277

Gnomad ASJ

AF:

0.00242

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00226

Gnomad FIN

AF:

0.00696

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00572

Gnomad OTH

AF:

0.00207

GnomAD3 exomes

AF:

0.00277

AC:

452

AN:

163130

Hom.:

AF XY:

0.00295

AC XY:

271

AN XY:

91822

show subpopulations

Gnomad AFR exome

AF:

0.000480

Gnomad AMR exome

AF:

0.000160

Gnomad ASJ exome

AF:

0.00243

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00236

Gnomad FIN exome

AF:

0.00602

Gnomad NFE exome

AF:

0.00388

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00439

AC:

6023

AN:

1371184

Hom.:

Cov.:

AF XY:

0.00433

AC XY:

2947

AN XY:

679828

show subpopulations

Gnomad4 AFR exome

AF:

0.000551

Gnomad4 AMR exome

AF:

0.000244

Gnomad4 ASJ exome

AF:

0.00254

Gnomad4 EAS exome

AF:

0.0000285

Gnomad4 SAS exome

AF:

0.00259

Gnomad4 FIN exome

AF:

0.00620

Gnomad4 NFE exome

AF:

0.00500

Gnomad4 OTH exome

AF:

0.00258

GnomAD4 genome

AF:

0.00351

AC:

500

AN:

142352

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

236

AN XY:

69664

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.000276

Gnomad4 ASJ

AF:

0.00242

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00226

Gnomad4 FIN

AF:

0.00696

Gnomad4 NFE

AF:

0.00572

Gnomad4 OTH

AF:

0.00204

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	LORICRIN: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 27, 2023	- -

Loricrin keratoderma

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Aug 07, 2018

- -

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