rs861020

chr1-209803766-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006147.4(IRF6):c.-75-1723T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,198 control chromosomes in the GnomAD database, including 51,676 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 0.82 (51676 hom., cov: 33)
• Consequence: IRF6 NM_006147.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF6	NM_006147.4	c.-75-1723T>C		intron_variant		ENST00000367021.8
IRF6	NM_001206696.2	c.-112+2181T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF6	ENST00000367021.8	c.-75-1723T>C		intron_variant		1	NM_006147.4	P1
IRF6	ENST00000542854.5	c.-112+2181T>C		intron_variant		2
IRF6	ENST00000696134.1	c.-75-1723T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125225 AN: 152080 Hom.: 51646 Cov.: 33

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.834

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.823 AC: 125310 AN: 152198 Hom.: 51676 Cov.: 33 AF XY: 0.820 AC XY: 61002 AN XY: 74410

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.831

Alfa AF: 0.808 Hom.: 65539

Bravo AF: 0.829

Asia WGS AF: 0.762 AC: 2652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.7
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

Other links and lift over

dbSNP: rs861020; hg19: chr1-209977111;