1-209786741-TA-T

Position:

• chr1-209786741-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006147.4(IRF6):​c.*1678del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,178 control chromosomes in the GnomAD database, including 2,879 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2879 hom., cov: 27)
  • Failed GnomAD Quality Control
• Consequence: IRF6 NM_006147.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.405

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 -10 ACMG points.

• BP6: Variant 1-209786741-TA-T is Benign according to our data. Variant chr1-209786741-TA-T is described in ClinVar as [Benign]. Clinvar id is 295181.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF6	NM_006147.4	c.*1678del		3_prime_UTR_variant	9/9	ENST00000367021.8
IRF6	NM_001206696.2	c.*1678del		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF6	ENST00000367021.8	c.*1678del		3_prime_UTR_variant	9/9	1	NM_006147.4	P1
IRF6	ENST00000542854.5	c.*1678del		3_prime_UTR_variant	7/7	2
IRF6	ENST00000696134.1	c.*2509del		3_prime_UTR_variant, NMD_transcript_variant	9/9

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29299 AN: 152060 Hom.: 2876 Cov.: 27

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.188

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.193 AC: 29328 AN: 152178 Hom.: 2879 Cov.: 27 AF XY: 0.193 AC XY: 14342 AN XY: 74396

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.0903

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.186

Alfa AF: 0.203 Hom.: 323

Bravo AF: 0.193

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Cleft Lip +/- Cleft Palate, Autosomal Dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Van der Woude syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs141112353; hg19: chr1-209960086;