Variant 1-152910335-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005547.4(IVL):c.538G>A(p.Glu180Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,567,982 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 32 hom., cov: 31)

Exomes 𝑓: 0.00033 ( 4 hom. )

Consequence

IVL
NM_005547.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.08

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029917955).

BP6

Variant 1-152910335-G-A is Benign according to our data. Variant chr1-152910335-G-A is described in ClinVar as [Benign]. Clinvar id is 775601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0146 (2182/149922) while in subpopulation AFR AF= 0.0514 (2077/40420). AF 95% confidence interval is 0.0495. There are 32 homozygotes in gnomad4. There are 1019 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IVL	NM_005547.4 linkuse as main transcript	c.538G>A	p.Glu180Lys	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.538G>A	p.Glu180Lys	missense_variant	2/2	2	NM_005547.4	ENSP00000357753.3	P07476
ENSG00000289062	ENST00000686895.2 linkuse as main transcript	n.94+2706C>T		intron_variant
ENSG00000289062	ENST00000702923.1 linkuse as main transcript	n.238+2538C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2185

AN:

149800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0516

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000104

Gnomad OTH

AF:

0.0121

GnomAD3 exomes

AF:

0.00182

AC:

353

AN:

193814

Hom.:

AF XY:

0.00143

AC XY:

149

AN XY:

103902

show subpopulations

Gnomad AFR exome

AF:

0.0316

Gnomad AMR exome

AF:

0.000771

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000389

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.000194

GnomAD4 exome

AF:

0.000335

AC:

475

AN:

1418060

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

213

AN XY:

702356

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.000712

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000611

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000827

Gnomad4 OTH exome

AF:

0.000856

GnomAD4 genome

AF:

0.0146

AC:

2182

AN:

149922

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1019

AN XY:

73274

show subpopulations

Gnomad4 AFR

AF:

0.0514

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000104

Gnomad4 OTH

AF:

0.0120

Alfa

AF:

0.00627

Hom.:

ESP6500AA

AF:

0.0579

AC:

255

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00492

AC:

585

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.0

DANN

Benign

0.82

DEOGEN2

Benign

0.088

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.2

REVEL

Benign

0.061

Sift

Benign

0.18

Sift4G

Uncertain

0.019

Polyphen

0.63

Vest4

0.084

MVP

0.27

MPC

0.0045

ClinPred

0.011

GERP RS

0.14

Varity_R

0.076

gMVP

0.035

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