Variant 1-153261034-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000427.3(LORICRIN):c.85A>G(p.Ser29Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,469,178 control chromosomes in the GnomAD database, including 91,746 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.30 ( 6400 hom., cov: 30)

Exomes 𝑓: 0.36 ( 85346 hom. )

Consequence

LORICRIN
NM_000427.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.362

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029177964).

BP6

Variant 1-153261034-A-G is Benign according to our data. Variant chr1-153261034-A-G is described in ClinVar as [Benign]. Clinvar id is 1262705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-153261034-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LORICRIN	NM_000427.3 linkuse as main transcript	c.85A>G	p.Ser29Gly	missense_variant	2/2	ENST00000368742.4	NP_000418.2	P23490

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LORICRIN	ENST00000368742.4 linkuse as main transcript	c.85A>G	p.Ser29Gly	missense_variant	2/2	1	NM_000427.3	ENSP00000357731.3		P23490

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

41007

AN:

137344

Hom.:

6396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.0688

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.307

GnomAD3 exomes

AF:

0.286

AC:

56497

AN:

197866

Hom.:

8616

AF XY:

0.290

AC XY:

32051

AN XY:

110586

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.241

Gnomad ASJ exome

AF:

0.283

Gnomad EAS exome

AF:

0.0635

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.350

Gnomad NFE exome

AF:

0.357

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.362

AC:

482570

AN:

1331724

Hom.:

85346

Cov.:

AF XY:

0.358

AC XY:

237478

AN XY:

663044

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.0681

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.373

Gnomad4 NFE exome

AF:

0.395

Gnomad4 OTH exome

AF:

0.329

GnomAD4 genome

AF:

0.299

AC:

41033

AN:

137454

Hom.:

6400

Cov.:

AF XY:

0.295

AC XY:

19840

AN XY:

67224

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.275

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.0688

Gnomad4 SAS

AF:

0.235

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.393

Gnomad4 OTH

AF:

0.303

Alfa

AF:

0.330

Hom.:

2273

Bravo

AF:

0.259

TwinsUK

AF:

0.366

AC:

1356

ALSPAC

AF:

0.367

AC:

1413

ExAC

AF:

0.268

AC:

31707

Asia WGS

AF:

0.128

AC:

446

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.8

DANN

Benign

0.59

DEOGEN2

Benign

0.019

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0041

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PROVEAN

Benign

2.3

REVEL

Benign

0.11

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.26

ClinPred

0.0024

GERP RS

-4.0

Varity_R

0.10

gMVP

0.13

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