chr1-153261012-C-CGGCGGTGGCGGTGGCGGTGGCGGCGGCGGT

Variant names:

• chr1-153261012-C-CGGCGGTGGCGGTGGCGGTGGCGGCGGCGGT
• rs150026164
• NM_000427.3:c.80_81insTGGCGGCGGCGGTGGCGGTGGCGGTGGCGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_000427.3(LORICRIN):​c.80_81insTGGCGGCGGCGGTGGCGGTGGCGGTGGCGG​(p.Gly27_Gly28insGlyGlyGlyGlyGlyGlyGlyGlyGlyGly) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,421,096 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LORICRIN NM_000427.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• loricrin keratoderma

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000301414 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000427.3.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000427.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LORICRIN	NM_000427.3	MANE Select	c.80_81insTGGCGGCGGCGGTGGCGGTGGCGGTGGCGG	p.Gly27_Gly28insGlyGlyGlyGlyGlyGlyGlyGlyGlyGly	disruptive_inframe_insertion	Exon 2 of 2	NP_000418.2	P23490

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LORICRIN	ENST00000368742.4	TSL:1 MANE Select	c.80_81insTGGCGGCGGCGGTGGCGGTGGCGGTGGCGG	p.Gly27_Gly28insGlyGlyGlyGlyGlyGlyGlyGlyGlyGly	disruptive_inframe_insertion	Exon 2 of 2	ENSP00000357731.3	P23490
	ENSG00000301414	ENST00000778757.1		n.203+154_203+155insTGGCGGCGGCGGTGGCGGTGGCGGTGGCGG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1421096 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 706508

African (AFR) AF: 0.00 AC: 0 AN: 30260

American (AMR) AF: 0.00 AC: 0 AN: 41198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25098

East Asian (EAS) AF: 0.00 AC: 0 AN: 36476

South Asian (SAS) AF: 0.00 AC: 0 AN: 82372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090596

Other (OTH) AF: 0.00 AC: 0 AN: 58646

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs150026164; hg19: chr1-153233488;