NM_002016.2:c.139-84G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002016.2(FLG):​c.139-84G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,561,218 control chromosomes in the GnomAD database, including 4,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.098 (2488 hom., cov: 32)
  • Exomes 𝑓: 0.0099 (2030 hom.)
• Consequence: FLG NM_002016.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-152314831-C-G is Benign according to our data. Variant chr1-152314831-C-G is described in ClinVar as Benign. ClinVar VariationId is 1245429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLG	NM_002016.2	MANE Select	c.139-84G>C		intron	N/A	NP_002007.1	P20930
	CCDST	NR_103778.1		n.788C>G		non_coding_transcript_exon	Exon 2 of 7
	CCDST	NR_186761.1		n.578-17752C>G		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>C		intron	N/A	ENSP00000357789.1	P20930
	CCDST	ENST00000392688.7	TSL:2	n.788C>G		non_coding_transcript_exon	Exon 2 of 7
	CCDST	ENST00000665223.1		n.1671C>G		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14886 AN: 151700 Hom.: 2484 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00209

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0643

GnomAD4 exome AF: 0.00985 AC: 13883 AN: 1409398 Hom.: 2030 Cov.: 25 AF XY: 0.00843 AC XY: 5916 AN XY: 702070

African (AFR) AF: 0.350 AC: 11106 AN: 31752

American (AMR) AF: 0.0170 AC: 678 AN: 39876

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 36 AN: 25014

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

South Asian (SAS) AF: 0.000941 AC: 75 AN: 79672

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

Middle Eastern (MID) AF: 0.0111 AC: 62 AN: 5582

European-Non Finnish (NFE) AF: 0.000682 AC: 734 AN: 1076850

Other (OTH) AF: 0.0204 AC: 1192 AN: 58468

GnomAD4 genome AF: 0.0983 AC: 14921 AN: 151820 Hom.: 2488 Cov.: 32 AF XY: 0.0951 AC XY: 7053 AN XY: 74200

African (AFR) AF: 0.343 AC: 14181 AN: 41400

American (AMR) AF: 0.0337 AC: 513 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00188 AC: 9 AN: 4782

European-Finnish (FIN) AF: 0.0000949 AC: 1 AN: 10532

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00107 AC: 73 AN: 67980

Other (OTH) AF: 0.0636 AC: 134 AN: 2106

Alfa AF: 0.00457 Hom.: 8

Bravo AF: 0.109

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.087
DANN	Benign	0.37
PhyloP100		-1.4
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: rs3126082; hg19: chr1-152287307;