1-209803301-T-C

Position:

• chr1-209803301-T-C

Variant summary

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

The NM_006147.4(IRF6):​c.-75-1258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,048 control chromosomes in the GnomAD database, including 10,454 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 (10454 hom., cov: 32)
• Consequence: IRF6 NM_006147.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF6	NM_006147.4	c.-75-1258A>G		intron_variant		ENST00000367021.8	NP_006138.1
IRF6	NM_001206696.2	c.-112+2646A>G		intron_variant			NP_001193625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF6	ENST00000367021.8	c.-75-1258A>G		intron_variant		1	NM_006147.4	ENSP00000355988	P1
IRF6	ENST00000542854.5	c.-112+2646A>G		intron_variant		2		ENSP00000440532
IRF6	ENST00000696134.1	c.-75-1258A>G		intron_variant, NMD_transcript_variant				ENSP00000512427

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55235 AN: 151930 Hom.: 10452 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.363 AC: 55256 AN: 152048 Hom.: 10454 Cov.: 32 AF XY: 0.367 AC XY: 27314 AN XY: 74326

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.356

Alfa AF: 0.217 Hom.: 487

Bravo AF: 0.369

Asia WGS AF: 0.427 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.2
DANN	Benign	0.81

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: rs2073487; hg19: chr1-209976646; COSMIC: COSV65418954; COSMIC: COSV65418954;