rs2235373

chr1-209790458-G-Achr1-209790458-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006147.4(IRF6):c.1060+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,602,858 control chromosomes in the GnomAD database, including 36,009 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4035 hom., cov: 33)
  • Exomes 𝑓: 0.20 (31974 hom.)
• Consequence: IRF6 NM_006147.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.866

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-209790458-G-A is Benign according to our data. Variant chr1-209790458-G-A is described in ClinVar as [Benign]. Clinvar id is 1291060.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF6	NM_006147.4	c.1060+37C>T		intron_variant		ENST00000367021.8
IRF6	NM_001206696.2	c.775+37C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF6	ENST00000367021.8	c.1060+37C>T		intron_variant		1	NM_006147.4	P1
IRF6	ENST00000542854.5	c.775+37C>T		intron_variant		2
IRF6	ENST00000643798.1	c.*570+37C>T		intron_variant, NMD_transcript_variant
IRF6	ENST00000696134.1	c.*487+37C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32795 AN: 152088 Hom.: 4031 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.202

GnomAD3 exomes AF: 0.236 AC: 59067 AN: 250666 Hom.: 8376 AF XY: 0.230 AC XY: 31209 AN XY: 135624

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.348

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.483

Gnomad SAS exome AF: 0.297

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.198 AC: 287834 AN: 1450652 Hom.: 31974 Cov.: 30 AF XY: 0.200 AC XY: 144343 AN XY: 722336

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.343

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.468

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.216 AC: 32817 AN: 152206 Hom.: 4035 Cov.: 33 AF XY: 0.219 AC XY: 16262 AN XY: 74418

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.200

Alfa AF: 0.178 Hom.: 491

Bravo AF: 0.229

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.8
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: rs2235373; hg19: chr1-209963803; COSMIC: COSV65418889; COSMIC: COSV65418889;