chr1-153261012-C-CGGCGGT

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]

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
LORICRINNM_000427.3 linkc.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
LORICRINENST00000368742.4 linkc.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.:
24
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.:
32
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.:
24
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

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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.

Other links and lift over

dbSNP: rs150026164; hg19: chr1-153233488; API