1-153261012-CGGCGGT-CGGCGGTGGCGGTGGCGGTGGCGGCGGCGGTGGCGGT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 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. 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000427.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LORICRIN	NM_000427.3	c.80_81insTGGCGGCGGCGGTGGCGGTGGCGGTGGCGG	p.Gly27_Gly28insGlyGlyGlyGlyGlyGlyGlyGlyGlyGly	disruptive_inframe_insertion	Exon 2 of 2	ENST00000368742.4	NP_000418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LORICRIN	ENST00000368742.4	c.80_81insTGGCGGCGGCGGTGGCGGTGGCGGTGGCGG	p.Gly27_Gly28insGlyGlyGlyGlyGlyGlyGlyGlyGlyGly	disruptive_inframe_insertion	Exon 2 of 2	1	NM_000427.3	ENSP00000357731.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-153233488;