Variant chr1-152304869-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002016.2(FLG):c.10017G>A(p.Gln3339Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,646 control chromosomes in the GnomAD database, including 33,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 3149 hom., cov: 29)

Exomes 𝑓: 0.17 ( 30705 hom. )

Consequence

FLG
NM_002016.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.308

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-152304869-C-T is Benign according to our data. Variant chr1-152304869-C-T is described in ClinVar as [Benign]. Clinvar id is 2585647.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-152304869-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.308 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLG	NM_002016.2 linkuse as main transcript	c.10017G>A	p.Gln3339Gln	synonymous_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 linkuse as main transcript	c.10017G>A	p.Gln3339Gln	synonymous_variant	3/3	1	NM_002016.2	ENSP00000357789.1		P20930

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23751

AN:

151688

Hom.:

3146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.326

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.567

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.195

GnomAD3 exomes

AF:

0.243

AC:

61072

AN:

251484

Hom.:

10694

AF XY:

0.243

AC XY:

33022

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0290

Gnomad AMR exome

AF:

0.429

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.560

Gnomad SAS exome

AF:

0.371

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.173

AC:

253172

AN:

1461840

Hom.:

30705

Cov.:

AF XY:

0.178

AC XY:

129525

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0265

Gnomad4 AMR exome

AF:

0.418

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.560

Gnomad4 SAS exome

AF:

0.359

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.206

GnomAD4 genome

AF:

0.156

AC:

23751

AN:

151806

Hom.:

3149

Cov.:

AF XY:

0.168

AC XY:

12443

AN XY:

74136

show subpopulations

Gnomad4 AFR

AF:

0.0339

Gnomad4 AMR

AF:

0.327

Gnomad4 ASJ

AF:

0.292

Gnomad4 EAS

AF:

0.566

Gnomad4 SAS

AF:

0.377

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.192

Alfa

AF:

0.141

Hom.:

887

Bravo

AF:

0.166

Asia WGS

AF:

0.455

AC:

1579

AN:

3476

EpiCase

AF:

0.151

EpiControl

AF:

0.148

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ichthyosis vulgaris

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.37

DANN

Benign

0.32

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