Variant 1-209790458-G-A 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.1060+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,602,858 control chromosomes in the GnomAD database, including 36,009 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4035 hom., cov: 33)

Exomes 𝑓: 0.20 ( 31974 hom. )

Consequence

IRF6
NM_006147.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.866

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-209790458-G-A is Benign according to our data. Variant chr1-209790458-G-A is described in ClinVar as [Benign]. Clinvar id is 1291060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 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.1060+37C>T		intron_variant		ENST00000367021.8	NP_006138.1
IRF6	NM_001206696.2 linkuse as main transcript	c.775+37C>T		intron_variant			NP_001193625.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
IRF6	ENST00000367021.8 linkuse as main transcript	c.1060+37C>T	intron_variant	1	NM_006147.4	ENSP00000355988	P1	O14896-1
IRF6	ENST00000542854.5 linkuse as main transcript	c.775+37C>T	intron_variant	2		ENSP00000440532		O14896-2
IRF6	ENST00000643798.1 linkuse as main transcript	c.*570+37C>T	intron_variant, NMD_transcript_variant			ENSP00000496669
IRF6	ENST00000696134.1 linkuse as main transcript	c.*487+37C>T	intron_variant, NMD_transcript_variant			ENSP00000512427

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32795

AN:

152088

Hom.:

4031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.202

GnomAD3 exomes

AF:

0.236

AC:

59067

AN:

250666

Hom.:

8376

AF XY:

0.230

AC XY:

31209

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.232

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.483

Gnomad SAS exome

AF:

0.297

Gnomad FIN exome

AF:

0.135

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.198

AC:

287834

AN:

1450652

Hom.:

31974

Cov.:

AF XY:

0.200

AC XY:

144343

AN XY:

722336

show subpopulations

Gnomad4 AFR exome

AF:

0.236

Gnomad4 AMR exome

AF:

0.343

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.468

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.179

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.216

AC:

32817

AN:

152206

Hom.:

4035

Cov.:

AF XY:

0.219

AC XY:

16262

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.324

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.471

Gnomad4 SAS

AF:

0.307

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.172

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.178

Hom.:

491

Bravo

AF:

0.229

Asia WGS

AF:

0.329

AC:

1145

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.8

DANN

Benign

0.45

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