rs11204980

Positions:

• chr1-152323715-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002016.2(FLG):​c.-22+1474C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,152 control chromosomes in the GnomAD database, including 4,049 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (4049 hom., cov: 31)
• Consequence: FLG NM_002016.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835

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-AS1 (HGNC:27913): (cervical cancer associated DHX9 suppressive transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLG	NM_002016.2	c.-22+1474C>G		intron_variant		ENST00000368799.2
FLG-AS1	NR_103778.1	n.914+8758G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLG	ENST00000368799.2	c.-22+1474C>G		intron_variant		1	NM_002016.2	P1
FLG-AS1	ENST00000653548.1	n.390-8868G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30553 AN: 151036 Hom.: 4041 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.202 AC: 30574 AN: 151152 Hom.: 4049 Cov.: 31 AF XY: 0.214 AC XY: 15777 AN XY: 73828

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.230

Alfa AF: 0.169 Hom.: 324

Bravo AF: 0.213

Asia WGS AF: 0.505 AC: 1753 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs11204980; hg19: chr1-152296191;