Variant 1-152306400-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002016.2(FLG):c.8486G>A(p.Arg2829His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,601,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

FLG
NM_002016.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.703

Variant links:

Genes affected

FLG (HGNC:3748): (filaggrin) The protein encoded by this gene is an intermediate filament-associated protein that aggregates keratin intermediate filaments in mammalian epidermis. It is initially synthesized as a polyprotein precursor, profilaggrin (consisting of multiple filaggrin units of 324 aa each), which is localized in keratohyalin granules, and is subsequently proteolytically processed into individual functional filaggrin molecules. Mutations in this gene are associated with ichthyosis vulgaris.[provided by RefSeq, Dec 2009]

FLG links:

FLG-AS1 (HGNC:):

FLG-AS1 links:

CCDST (HGNC:55988): (cervical cancer associated DHX9 suppressive transcript)

CCDST links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0065229833).

BP6

Variant 1-152306400-C-T is Benign according to our data. Variant chr1-152306400-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 599456.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLG	NM_002016.2 link	c.8486G>A	p.Arg2829His	missense_variant	3/3	ENST00000368799.2	NP_002007.1	P20930

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLG	ENST00000368799.2 link	c.8486G>A	p.Arg2829His	missense_variant	3/3	1	NM_002016.2	ENSP00000357789.1		P20930

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

161

AN:

141674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00106

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00107

AC:

267

AN:

250680

Hom.:

AF XY:

0.00102

AC XY:

138

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.00486

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00118

AC:

1719

AN:

1459352

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

810

AN XY:

726110

show subpopulations

Gnomad4 AFR exome

AF:

0.00539

Gnomad4 AMR exome

AF:

0.000448

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000506

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00114

AC:

161

AN:

141774

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

AN XY:

69478

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00106

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00201

Hom.:

ExAC

AF:

0.00111

AC:

134

EpiCase

AF:

0.00169

EpiControl

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital

Jul 17, 2017

BS1, BP1, BP4; This alteration has an allele frequency that is greater than expected for the associated disease, is a missense alteration in a gene for which primarily truncating variants are known to cause disease, and is predicted to be tolerated by multiple functional prediction tools. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.11

DANN

Benign

0.53

DEOGEN2

Benign

0.013

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.00012

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.045

PrimateAI

Benign

0.20

PROVEAN

Benign

1.0

REVEL

Benign

0.0090

Sift

Benign

1.0

Polyphen

0.0010

Vest4

0.066

MVP

0.061

ClinPred

0.0013

GERP RS

-5.7

Varity_R

0.015

gMVP

0.089

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