1-153261102-C-T

Variant names:

• chr1-153261102-C-T
• rs1143389
• NM_000427.3:c.153C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000427.3(LORICRIN):​c.153C>T​(p.Cys51Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,423,500 control chromosomes in the GnomAD database, including 23,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1869 hom., cov: 28)
  • Exomes 𝑓: 0.17 (21192 hom.)
• Consequence: LORICRIN NM_000427.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.975
• Publications: 8 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-153261102-C-T is Benign according to our data. Variant chr1-153261102-C-T is described in ClinVar as Benign. ClinVar VariationId is 1266330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.975 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

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.153C>T	p.Cys51Cys	synonymous	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.153C>T	p.Cys51Cys	synonymous	Exon 2 of 2	ENSP00000357731.3	P23490
	ENSG00000301414	ENST00000778757.1		n.203+227C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20537 AN: 149666 Hom.: 1870 Cov.: 28

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.292

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.174

GnomAD2 exomes AF: 0.291 AC: 15280 AN: 52420 AF XY: 0.310

Gnomad AFR exome AF: 0.0704

Gnomad AMR exome AF: 0.189

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.438

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.279

GnomAD4 exome AF: 0.169 AC: 214908 AN: 1273732 Hom.: 21192 Cov.: 48 AF XY: 0.177 AC XY: 110308 AN XY: 624820

African (AFR) AF: 0.0388 AC: 994 AN: 25628

American (AMR) AF: 0.155 AC: 3070 AN: 19770

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 5253 AN: 20260

East Asian (EAS) AF: 0.377 AC: 10995 AN: 29160

South Asian (SAS) AF: 0.385 AC: 24537 AN: 63672

European-Finnish (FIN) AF: 0.129 AC: 4429 AN: 34410

Middle Eastern (MID) AF: 0.291 AC: 1202 AN: 4134

European-Non Finnish (NFE) AF: 0.151 AC: 154808 AN: 1024140

Other (OTH) AF: 0.183 AC: 9620 AN: 52558

GnomAD4 genome AF: 0.137 AC: 20521 AN: 149768 Hom.: 1869 Cov.: 28 AF XY: 0.142 AC XY: 10394 AN XY: 73048

African (AFR) AF: 0.0404 AC: 1645 AN: 40734

American (AMR) AF: 0.154 AC: 2319 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 870 AN: 3438

East Asian (EAS) AF: 0.321 AC: 1598 AN: 4978

South Asian (SAS) AF: 0.377 AC: 1766 AN: 4680

European-Finnish (FIN) AF: 0.122 AC: 1252 AN: 10294

Middle Eastern (MID) AF: 0.303 AC: 88 AN: 290

European-Non Finnish (NFE) AF: 0.156 AC: 10503 AN: 67292

Other (OTH) AF: 0.174 AC: 358 AN: 2062

Alfa AF: 0.157 Hom.: 733

Bravo AF: 0.130

Asia WGS AF: 0.306 AC: 1054 AN: 3458

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.5
DANN	Benign	0.74
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1143389; hg19: chr1-153233578; COSMIC: COSV64201343;