chr1-152314831-C-T

Variant names:

• chr1-152314831-C-T
• rs3126082
• NM_002016.2:c.139-84G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002016.2(FLG):​c.139-84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000355 in 1,409,430 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: FLG NM_002016.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLG	NM_002016.2	MANE Select	c.139-84G>A		intron	N/A	NP_002007.1	P20930
	CCDST	NR_103778.1		n.788C>T		non_coding_transcript_exon	Exon 2 of 7
	CCDST	NR_186761.1		n.578-17752C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLG	ENST00000368799.2	TSL:1 MANE Select	c.139-84G>A		intron	N/A	ENSP00000357789.1	P20930
	CCDST	ENST00000392688.7	TSL:2	n.788C>T		non_coding_transcript_exon	Exon 2 of 7
	CCDST	ENST00000665223.1		n.1671C>T		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000355 AC: 5 AN: 1409430 Hom.: 0 Cov.: 25 AF XY: 0.00000285 AC XY: 2 AN XY: 702080

African (AFR) AF: 0.00 AC: 0 AN: 31780

American (AMR) AF: 0.0000251 AC: 1 AN: 39876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39444

South Asian (SAS) AF: 0.00 AC: 0 AN: 79672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1076850

Other (OTH) AF: 0.00 AC: 0 AN: 58472

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.18
PhyloP100		-1.4

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: rs3126082; hg19: chr1-152287307;