rs2294408

Positions:

• chr1-209800204-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729

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=-0.87).
• 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
IRF6	NM_006147.4	c.174+1036C>T		intron_variant		ENST00000367021.8
IRF6	NM_001206696.2	c.-111-3652C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF6	ENST00000367021.8	c.174+1036C>T		intron_variant		1	NM_006147.4	P1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55512 AN: 151924 Hom.: 10532 Cov.: 32

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

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

Other links and lift over

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