rs2294408

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006147.4(IRF6):​c.174+1036C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,042 control chromosomes in the GnomAD database, including 10,536 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10536 hom., cov: 32)

Consequence

IRF6
NM_006147.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.729
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IRF6NM_006147.4 linkuse as main transcriptc.174+1036C>T intron_variant ENST00000367021.8
IRF6NM_001206696.2 linkuse as main transcriptc.-111-3652C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IRF6ENST00000367021.8 linkuse as main transcriptc.174+1036C>T intron_variant 1 NM_006147.4 P1O14896-1

Frequencies

GnomAD3 genomes
AF:
0.365
AC:
55512
AN:
151924
Hom.:
10532
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.280
Gnomad AMI
AF:
0.392
Gnomad AMR
AF:
0.495
Gnomad ASJ
AF:
0.322
Gnomad EAS
AF:
0.568
Gnomad SAS
AF:
0.430
Gnomad FIN
AF:
0.365
Gnomad MID
AF:
0.354
Gnomad NFE
AF:
0.370
Gnomad OTH
AF:
0.361
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.365
AC:
55538
AN:
152042
Hom.:
10536
Cov.:
32
AF XY:
0.369
AC XY:
27455
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.280
Gnomad4 AMR
AF:
0.496
Gnomad4 ASJ
AF:
0.322
Gnomad4 EAS
AF:
0.567
Gnomad4 SAS
AF:
0.430
Gnomad4 FIN
AF:
0.365
Gnomad4 NFE
AF:
0.370
Gnomad4 OTH
AF:
0.357
Alfa
AF:
0.356
Hom.:
1192
Bravo
AF:
0.371
Asia WGS
AF:
0.426
AC:
1482
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.77
DANN
Benign
0.68

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.

Other links and lift over

dbSNP: rs2294408; hg19: chr1-209973549; COSMIC: COSV65418934; API