NM_002016.2:c.*179C>A

Variant names:

• chr1-152302521-G-T
• rs12071181
• NM_002016.2:c.*179C>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.*179C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FLG NM_002016.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 1 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=-0.89).

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.*179C>A		3_prime_UTR	Exon 3 of 3	NP_002007.1	P20930
	CCDST	NR_186761.1		n.578-30062G>T		intron	N/A
	CCDST	NR_186762.1		n.180-30062G>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.*179C>A		3_prime_UTR	Exon 3 of 3	ENSP00000357789.1	P20930
	CCDST	ENST00000420707.5	TSL:5	n.462+688G>T		intron	N/A
	CCDST	ENST00000593011.5	TSL:4	n.376+688G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 607234 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 315186

African (AFR) AF: 0.00 AC: 0 AN: 15166

American (AMR) AF: 0.00 AC: 0 AN: 18886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14662

East Asian (EAS) AF: 0.00 AC: 0 AN: 31698

South Asian (SAS) AF: 0.00 AC: 0 AN: 47454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2256

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 416180

Other (OTH) AF: 0.00 AC: 0 AN: 31128

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.015
DANN	Benign	0.42
PhyloP100		-3.0

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: rs12071181; hg19: chr1-152274997;