rs1143389

Variant names:

• chr1-153261102-C-A
• NM_000427.3:c.153C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-153261102-C-A
• chr1-153261102-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_000427.3(LORICRIN):​c.153C>A​(p.Cys51*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000785 in 1,273,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. C51C) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: LORICRIN NM_000427.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975

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 Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LORICRIN	NM_000427.3	c.153C>A	p.Cys51*	stop_gained	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.153C>A	p.Cys51*	stop_gained	Exon 2 of 2	1	NM_000427.3	ENSP00000357731.3

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 7.85e-7 AC: 1 AN: 1273904 Hom.: 0 Cov.: 48 AF XY: 0.00000160 AC XY: 1 AN XY: 624920

Gnomad4 AFR exome AF: 0.0000390

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Benign	-0.55
CADD	Pathogenic	28
DANN	Benign	0.91
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.20	N
Vest4		0.55
GERP RS		-7.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr1-153233578;