Variant 1-209792242-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF6	NM_006147.4 linkuse as main transcript	c.667+27C>G		intron_variant		ENST00000367021.8	NP_006138.1
IRF6	NM_001206696.2 linkuse as main transcript	c.382+27C>G		intron_variant			NP_001193625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF6	ENST00000367021.8 linkuse as main transcript	c.667+27C>G		intron_variant		1	NM_006147.4	ENSP00000355988	P1	O14896-1

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

GnomAD3 exomes

AF:

0.410

AC:

103035

AN:

251268

Hom.:

22359

AF XY:

0.403

AC XY:

54769

AN XY:

135830

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 SAS exome

AF:

0.417

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

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.550

Gnomad4 ASJ exome

AF:

0.308

Gnomad4 EAS exome

AF:

0.568

Gnomad4 SAS exome

AF:

0.414

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.375

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.367

AC:

55864

AN:

152092

Hom.:

10639

Cov.:

AF XY:

0.371

AC XY:

27592

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.288

Gnomad4 AMR

AF:

0.494

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.565

Gnomad4 SAS

AF:

0.432

Gnomad4 FIN

AF:

0.366

Gnomad4 NFE

AF:

0.370

Gnomad4 OTH

AF:

0.356

Alfa

AF:

0.273

Hom.:

1041

Bravo

AF:

0.374

Asia WGS

AF:

0.428

AC:

1492

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.4

DANN

Benign

0.52

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

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