Variant chr1-153261093-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000368742.4(LORICRIN):c.144T>C(p.Gly48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,424,686 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00067 ( 1 hom., cov: 29)

Exomes 𝑓: 0.000092 ( 1 hom. )

Consequence

LORICRIN
ENST00000368742.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.28

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-153261093-T-C is Benign according to our data. Variant chr1-153261093-T-C is described in ClinVar as [Benign]. Clinvar id is 2754030.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.28 with no splicing effect.

BS2

High AC in GnomAd4 at 91 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LORICRIN	NM_000427.3 linkuse as main transcript	c.144T>C	p.Gly48=	synonymous_variant	2/2	ENST00000368742.4	NP_000418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LORICRIN	ENST00000368742.4 linkuse as main transcript	c.144T>C	p.Gly48=	synonymous_variant	2/2	1	NM_000427.3	ENSP00000357731	P1

Frequencies

GnomAD3 genomes

AF:

0.000666

AC:

AN:

135172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000217

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00110

GnomAD3 exomes

AF:

0.0000968

AC:

AN:

82648

Hom.:

AF XY:

0.000128

AC XY:

AN XY:

47004

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.0000700

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000185

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000923

AC:

119

AN:

1289398

Hom.:

Cov.:

AF XY:

0.0000961

AC XY:

AN XY:

634806

show subpopulations

Gnomad4 AFR exome

AF:

0.00329

Gnomad4 AMR exome

AF:

0.000276

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000432

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.77e-7

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000673

AC:

AN:

135288

Hom.:

Cov.:

AF XY:

0.000590

AC XY:

AN XY:

66142

show subpopulations

Gnomad4 AFR

AF:

0.00240

Gnomad4 AMR

AF:

0.000217

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00108

Alfa

AF:

0.000555

Hom.:

Bravo

AF:

0.000748

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.7

DANN

Benign

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over