rs2236906

chr1-209798140-T-G

Variant summary

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

The NM_006147.4(IRF6):c.175-1588A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,014 control chromosomes in the GnomAD database, including 12,428 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 0.40 (12428 hom., cov: 32)
• Consequence: IRF6 NM_006147.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF6	NM_006147.4	c.175-1588A>C		intron_variant		ENST00000367021.8
IRF6	NM_001206696.2	c.-111-1588A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF6	ENST00000367021.8	c.175-1588A>C		intron_variant		1	NM_006147.4	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60573 AN: 151896 Hom.: 12418 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.399 AC: 60620 AN: 152014 Hom.: 12428 Cov.: 32 AF XY: 0.395 AC XY: 29319 AN XY: 74302

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.428

Alfa AF: 0.423 Hom.: 6382

Bravo AF: 0.391

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.52
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2236906; hg19: chr1-209971485;