rs2235375

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006147.4(IRF6):c.667+27C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,604,424 control chromosomes in the GnomAD database, including 120,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10639 hom., cov: 33)

Exomes 𝑓: 0.38 ( 109958 hom. )

Consequence

IRF6
NM_006147.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0730

Publications

37 publications found

Variant links:

Genes affected

IRF6 (HGNC:6121): (interferon regulatory factor 6) This gene encodes a member of the interferon regulatory transcription factor (IRF) family. Family members share a highly-conserved N-terminal helix-turn-helix DNA-binding domain and a less conserved C-terminal protein-binding domain. The encoded protein may be a transcriptional activator. Mutations in this gene can cause van der Woude syndrome and popliteal pterygium syndrome. Mutations in this gene are also associated with non-syndromic orofacial cleft type 6. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2011]

IRF6 Gene-Disease associations (from GenCC):

autosomal dominant popliteal pterygium syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
IRF6-related condition
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
van der Woude syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
popliteal pterygium syndrome
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
tooth agenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
van der Woude syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
orofacial cleft 6, susceptibility to
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

IRF6 links:

ENSG00000289700 (HGNC:):

ENSG00000289700 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-209792242-G-C is Benign according to our data. Variant chr1-209792242-G-C is described in ClinVar as Benign. ClinVar VariationId is 259926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006147.4. 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
	IRF6	NM_006147.4	MANE Select	c.667+27C>G		intron	N/A	NP_006138.1	G0Z349
	IRF6	NM_001206696.2		c.382+27C>G		intron	N/A	NP_001193625.1	O14896-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IRF6	ENST00000367021.8	TSL:1 MANE Select	c.667+27C>G	intron	N/A	ENSP00000355988.3	O14896-1
ENSG00000289700	ENST00000696133.1		c.667+27C>G	intron	N/A	ENSP00000512426.1	A0A8Q3SJ75
IRF6	ENST00000863915.1		c.667+27C>G	intron	N/A	ENSP00000533974.1

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55841

AN:

151974

Hom.:

10636

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.566

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.360

GnomAD2 exomes

AF:

0.410

AC:

103035

AN:

251268

AF XY:

0.403

show subpopulations

Gnomad AFR exome

AF:

0.283

Gnomad AMR exome

AF:

0.558

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.572

Gnomad FIN exome

AF:

0.373

Gnomad NFE exome

AF:

0.373

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.385

AC:

558705

AN:

1452332

Hom.:

109958

Cov.:

AF XY:

0.385

AC XY:

278146

AN XY:

723114

show subpopulations

African (AFR)

AF:

0.283

AC:

9422

AN:

33286

American (AMR)

AF:

0.550

AC:

24583

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

8027

AN:

26086

East Asian (EAS)

AF:

0.568

AC:

22498

AN:

39638

South Asian (SAS)

AF:

0.414

AC:

35602

AN:

86068

European-Finnish (FIN)

AF:

0.379

AC:

20218

AN:

53370

Middle Eastern (MID)

AF:

0.321

AC:

1844

AN:

5742

European-Non Finnish (NFE)

AF:

0.375

AC:

414032

AN:

1103342

Other (OTH)

AF:

0.374

AC:

22479

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

15272

30544

45815

61087

76359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13168

26336

39504

52672

65840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.367

AC:

55864

AN:

152092

Hom.:

10639

Cov.:

AF XY:

0.371

AC XY:

27592

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.288

AC:

11946

AN:

41476

American (AMR)

AF:

0.494

AC:

7556

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

1109

AN:

3468

East Asian (EAS)

AF:

0.565

AC:

2920

AN:

5170

South Asian (SAS)

AF:

0.432

AC:

2083

AN:

4826

European-Finnish (FIN)

AF:

0.366

AC:

3872

AN:

10578

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.370

AC:

25163

AN:

67976

Other (OTH)

AF:

0.356

AC:

751

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1837

3675

5512

7350

9187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.273

Hom.:

1041

Bravo

AF:

0.374

Asia WGS

AF:

0.428

AC:

1492

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Autosomal dominant popliteal pterygium syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.4

(source)

DANN

Benign

0.52

PhyloP100

0.073

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over