rs2013162

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006147.4(IRF6):c.459G>T(p.Ser153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,613,602 control chromosomes in the GnomAD database, including 121,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10526 hom., cov: 32)

Exomes 𝑓: 0.39 ( 110534 hom. )

Consequence

IRF6
NM_006147.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.72

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 1-209795339-C-A is Benign according to our data. Variant chr1-209795339-C-A is described in ClinVar as [Benign]. Clinvar id is 259925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-209795339-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.72 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF6	NM_006147.4 linkuse as main transcript	c.459G>T	p.Ser153=	synonymous_variant	5/9	ENST00000367021.8	NP_006138.1
IRF6	NM_001206696.2 linkuse as main transcript	c.174G>T	p.Ser58=	synonymous_variant	3/7		NP_001193625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF6	ENST00000367021.8 linkuse as main transcript	c.459G>T	p.Ser153=	synonymous_variant	5/9	1	NM_006147.4	ENSP00000355988	P1	O14896-1

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55499

AN:

151972

Hom.:

10523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.567

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.361

GnomAD3 exomes

AF:

0.410

AC:

103019

AN:

251410

Hom.:

22367

AF XY:

0.403

AC XY:

54724

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.275

Gnomad AMR exome

AF:

0.560

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.573

Gnomad SAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.373

Gnomad NFE exome

AF:

0.373

Gnomad OTH exome

AF:

0.372

GnomAD4 exome

AF:

0.385

AC:

562690

AN:

1461512

Hom.:

110534

Cov.:

AF XY:

0.385

AC XY:

279808

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.552

Gnomad4 ASJ exome

AF:

0.308

Gnomad4 EAS exome

AF:

0.569

Gnomad4 SAS exome

AF:

0.412

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.365

AC:

55523

AN:

152090

Hom.:

10526

Cov.:

AF XY:

0.369

AC XY:

27445

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.495

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.566

Gnomad4 SAS

AF:

0.430

Gnomad4 FIN

AF:

0.366

Gnomad4 NFE

AF:

0.370

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.359

Hom.:

18386

Bravo

AF:

0.371

Asia WGS

AF:

0.425

AC:

1480

AN:

3478

EpiCase

AF:

0.365

EpiControl

AF:

0.362

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal dominant popliteal pterygium syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Van der Woude syndrome;C0265259:Popliteal pterygium syndrome;C1837213:Orofacial cleft 6, susceptibility to

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Orofacial cleft 6, susceptibility to

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Van der Woude syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.29

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over