rs17317411

Variant names:

• chr1-209787969-T-C
• rs17317411
• NM_006147.4:c.*451A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006147.4(IRF6):​c.*451A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 200,636 control chromosomes in the GnomAD database, including 1,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1155 hom., cov: 32)
  • Exomes 𝑓: 0.12 (464 hom.)
• Consequence: IRF6 NM_006147.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.309
• Publications: 7 publications found

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]

IRF6 Gene-Disease associations (from GenCC):

• autosomal dominant popliteal pterygium syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• IRF6-related condition

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• van der Woude syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• popliteal pterygium syndrome

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• van der Woude syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• orofacial cleft 6, susceptibility to

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000289700 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-209787969-T-C is Benign according to our data. Variant chr1-209787969-T-C is described in ClinVar as Benign. ClinVar VariationId is 295199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006147.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF6	NM_006147.4	MANE Select	c.*451A>G		3_prime_UTR	Exon 9 of 9	NP_006138.1	G0Z349
	IRF6	NM_001206696.2		c.*451A>G		3_prime_UTR	Exon 7 of 7	NP_001193625.1	O14896-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF6	ENST00000367021.8	TSL:1 MANE Select	c.*451A>G		3_prime_UTR	Exon 9 of 9	ENSP00000355988.3	O14896-1
	ENSG00000289700	ENST00000696133.1		c.1400+455A>G		intron	N/A	ENSP00000512426.1	A0A8Q3SJ75
	IRF6	ENST00000863915.1		c.*451A>G		3_prime_UTR	Exon 8 of 8	ENSP00000533974.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16314 AN: 151928 Hom.: 1158 Cov.: 32

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0874

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.120 AC: 5833 AN: 48590 Hom.: 464 Cov.: 0 AF XY: 0.121 AC XY: 3083 AN XY: 25434

African (AFR) AF: 0.0252 AC: 20 AN: 794

American (AMR) AF: 0.0853 AC: 304 AN: 3562

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 73 AN: 978

East Asian (EAS) AF: 0.0340 AC: 88 AN: 2590

South Asian (SAS) AF: 0.160 AC: 1064 AN: 6660

European-Finnish (FIN) AF: 0.101 AC: 236 AN: 2328

Middle Eastern (MID) AF: 0.0616 AC: 9 AN: 146

European-Non Finnish (NFE) AF: 0.131 AC: 3791 AN: 29038

Other (OTH) AF: 0.0994 AC: 248 AN: 2494

GnomAD4 genome AF: 0.107 AC: 16306 AN: 152046 Hom.: 1155 Cov.: 32 AF XY: 0.106 AC XY: 7895 AN XY: 74316

African (AFR) AF: 0.0299 AC: 1242 AN: 41498

American (AMR) AF: 0.114 AC: 1743 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0874 AC: 303 AN: 3466

East Asian (EAS) AF: 0.0404 AC: 209 AN: 5172

South Asian (SAS) AF: 0.187 AC: 900 AN: 4824

European-Finnish (FIN) AF: 0.113 AC: 1187 AN: 10536

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10303 AN: 67972

Other (OTH) AF: 0.114 AC: 241 AN: 2108

Alfa AF: 0.127 Hom.: 700

Bravo AF: 0.100

Asia WGS AF: 0.105 AC: 369 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Orofacial cleft 6, susceptibility to (1)
-	-	1	Van der Woude syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17317411; hg19: chr1-209961314; COSMIC: COSV54213602; COSMIC: COSV54213602;