Variant chr1-152910384-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_005547.4(IVL):c.587C>T(p.Pro196Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000479 in 605,236 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

IVL
NM_005547.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.791

Variant links:

Genes affected

IVL (HGNC:6187): (involucrin) Involucrin, a component of the keratinocyte crosslinked envelope, is found in the cytoplasm and crosslinked to membrane proteins by transglutaminase. This gene is mapped to 1q21, among calpactin I light chain, trichohyalin, profillaggrin, loricrin, and calcyclin. [provided by RefSeq, Jul 2008]

IVL links:

ENSG00000289062 (HGNC:):

ENSG00000289062 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009338826).

BP6

Variant 1-152910384-C-T is Benign according to our data. Variant chr1-152910384-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2237203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IVL	NM_005547.4 linkuse as main transcript	c.587C>T	p.Pro196Leu	missense_variant	2/2	ENST00000368764.4	NP_005538.2	P07476

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IVL	ENST00000368764.4 linkuse as main transcript	c.587C>T	p.Pro196Leu	missense_variant	2/2	2	NM_005547.4	ENSP00000357753.3	P07476
ENSG00000289062	ENST00000686895.2 linkuse as main transcript	n.94+2657G>A		intron_variant
ENSG00000289062	ENST00000702923.1 linkuse as main transcript	n.238+2489G>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000646

AC:

AN:

128450

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000228

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000245

Gnomad SAS

AF:

0.000264

Gnomad FIN

AF:

0.000121

Gnomad MID

AF:

0.00625

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.00177

GnomAD3 exomes

AF:

0.000826

AC:

AN:

49654

Hom.:

AF XY:

0.000853

AC XY:

AN XY:

23450

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00228

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00132

Gnomad OTH exome

AF:

0.00318

GnomAD4 exome

AF:

0.000434

AC:

207

AN:

476702

Hom.:

Cov.:

AF XY:

0.000449

AC XY:

114

AN XY:

253886

show subpopulations

Gnomad4 AFR exome

AF:

0.000167

Gnomad4 AMR exome

AF:

0.000749

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000337

Gnomad4 SAS exome

AF:

0.000133

Gnomad4 FIN exome

AF:

0.000114

Gnomad4 NFE exome

AF:

0.000562

Gnomad4 OTH exome

AF:

0.000673

GnomAD4 genome

AF:

0.000646

AC:

AN:

128534

Hom.:

Cov.:

AF XY:

0.000558

AC XY:

AN XY:

62672

show subpopulations

Gnomad4 AFR

AF:

0.000256

Gnomad4 AMR

AF:

0.000227

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000246

Gnomad4 SAS

AF:

0.000265

Gnomad4 FIN

AF:

0.000121

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.00175

Alfa

AF:

0.00101

Hom.:

ExAC

AF:

0.000297

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

IVL: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.027

DANN

Benign

0.44

DEOGEN2

Benign

0.055

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.48

M_CAP

Benign

0.0081

MetaRNN

Benign

0.0093

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.55

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.78

REVEL

Benign

0.0090

Sift

Benign

0.21

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.080

MVP

0.24

MPC

0.0048

ClinPred

0.017

GERP RS

-3.7

Varity_R

0.022

gMVP

0.012

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