1-209802041-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006147.4(IRF6):c.-73T>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,032 control chromosomes in the GnomAD database, including 14,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14703 hom., cov: 32)

Exomes 𝑓: 0.50 ( 8 hom. )

Consequence

IRF6
NM_006147.4 splice_region

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.207

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:

ENSG00000289700 (HGNC:):

ENSG00000289700 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=-0.89).

BP6

Variant 1-209802041-A-G is Benign according to our data. Variant chr1-209802041-A-G is described in ClinVar as [Benign]. Clinvar id is 295214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IRF6	NM_006147.4 link	c.-73T>C	splice_region_variant	Exon 2 of 9	ENST00000367021.8	NP_006138.1	O14896-1G0Z349
IRF6	NM_006147.4 link	c.-73T>C	5_prime_UTR_variant	Exon 2 of 9	ENST00000367021.8	NP_006138.1	O14896-1G0Z349
IRF6	NM_001206696.2 link	c.-112+3906T>C	intron_variant	Intron 1 of 6		NP_001193625.1	O14896-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IRF6	ENST00000367021.8 link	c.-73T>C	splice_region_variant	Exon 2 of 9	1	NM_006147.4	ENSP00000355988.3	O14896-1
ENSG00000289700	ENST00000696133.1 link	c.-73T>C	splice_region_variant	Exon 2 of 10			ENSP00000512426.1	A0A8Q3SJ75
IRF6	ENST00000367021.8 link	c.-73T>C	5_prime_UTR_variant	Exon 2 of 9	1	NM_006147.4	ENSP00000355988.3	O14896-1
ENSG00000289700	ENST00000696133.1 link	c.-73T>C	5_prime_UTR_variant	Exon 2 of 10			ENSP00000512426.1	A0A8Q3SJ75

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65741

AN:

151866

Hom.:

14686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.452

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.531

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.475

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.433

AC:

65802

AN:

151984

Hom.:

14703

Cov.:

AF XY:

0.427

AC XY:

31678

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.505

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.519

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.350

Gnomad4 FIN

AF:

0.393

Gnomad4 NFE

AF:

0.433

Gnomad4 OTH

AF:

0.453

Alfa

AF:

0.436

Hom.:

14626

Bravo

AF:

0.430

Asia WGS

AF:

0.333

AC:

1156

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Dec 30, 2019

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Orofacial cleft 6, susceptibility to

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Van der Woude syndrome 1

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

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