rs2236907

chr1-209798283-C-Achr1-209798283-C-Gchr1-209798283-C-T

Variant summary

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

The NM_006147.4(IRF6):c.175-1731G>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 152,066 control chromosomes in the GnomAD database, including 10,513 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 0.36 (10513 hom., cov: 33)
• Consequence: IRF6 NM_006147.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF6	NM_006147.4	c.175-1731G>T		intron_variant		ENST00000367021.8
IRF6	NM_001206696.2	c.-111-1731G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF6	ENST00000367021.8	c.175-1731G>T		intron_variant		1	NM_006147.4	P1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55474 AN: 151946 Hom.: 10509 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.365 AC: 55500 AN: 152066 Hom.: 10513 Cov.: 33 AF XY: 0.369 AC XY: 27423 AN XY: 74320

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.358

Alfa AF: 0.236 Hom.: 540

Bravo AF: 0.371

Asia WGS AF: 0.425 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.7
Dann	Benign	0.48

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: rs2236907; hg19: chr1-209971628; COSMIC: COSV65418914;