rs11204980

Variant names:

• chr1-152323715-G-C
• rs11204980
• NM_002016.2:c.-22+1474C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002016.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLG	NM_002016.2	MANE Select	c.-22+1474C>G		intron	N/A	NP_002007.1
	CCDST	NR_103778.1		n.914+8758G>C		intron	N/A
	CCDST	NR_186761.1		n.578-8868G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLG	ENST00000368799.2	TSL:1 MANE Select	c.-22+1474C>G		intron	N/A	ENSP00000357789.1
	CCDST	ENST00000392688.7	TSL:2	n.914+8758G>C		intron	N/A
	CCDST	ENST00000420707.5	TSL:5	n.514+8758G>C		intron	N/A

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

African (AFR) AF: 0.133 AC: 5493 AN: 41276

American (AMR) AF: 0.358 AC: 5422 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1088 AN: 3460

East Asian (EAS) AF: 0.597 AC: 3047 AN: 5106

South Asian (SAS) AF: 0.434 AC: 2087 AN: 4806

European-Finnish (FIN) AF: 0.188 AC: 1967 AN: 10474

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.159 AC: 10732 AN: 67602

Other (OTH) AF: 0.230 AC: 480 AN: 2090

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.48
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11204980; hg19: chr1-152296191;