rs150026164

Variant names:

• chr1-153261012-CGGCGGT-C
• rs150026164
• NM_000427.3:c.75_80delTGGCGG

Your query was ambiguous. Multiple possible variants found:

• chr1-153261012-CGGCGGT-C
• chr1-153261012-CGGCGGT-CGGCGGTGGCGGT
• chr1-153261012-CGGCGGT-CGGCGGTGGCGGTGGCGGTGGCGGCGGCGGTGGCGGT
• chr1-153261012-CGGCGGT-CGGCGGTGGCGGTGGCGGT
• chr1-153261012-CGGCGGT-CGGCGGTGGCGGTGGCGGTGGCGGT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_000427.3(LORICRIN):​c.75_80delTGGCGG​(p.Gly26_Gly27del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000281 in 1,421,080 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: 0.0000028 (0 hom.)
• Consequence: LORICRIN NM_000427.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.68
• Publications: 6 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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.75_80delTGGCGG	p.Gly26_Gly27del	disruptive_inframe_deletion	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.75_80delTGGCGG	p.Gly26_Gly27del	disruptive_inframe_deletion	Exon 2 of 2	ENSP00000357731.3	P23490
	ENSG00000301414	ENST00000778757.1		n.203+149_203+154delTGGCGG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000281 AC: 4 AN: 1421080 Hom.: 0 AF XY: 0.00000283 AC XY: 2 AN XY: 706498

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.0000243 AC: 1 AN: 41198

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

East Asian (EAS) AF: 0.0000274 AC: 1 AN: 36476

South Asian (SAS) AF: 0.00 AC: 0 AN: 82364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50780

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

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090592

Other (OTH) AF: 0.0000171 AC: 1 AN: 58644

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0236461), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7

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;