rs861019

Positions:

• chr1-209802041-A-C
• chr1-209802041-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006147.4(IRF6):​c.-73T>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: IRF6 NM_006147.4 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207

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]

ENSG00000289700 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF6	NM_006147.4	c.-73T>G		splice_region_variant	2/9	ENST00000367021.8	NP_006138.1
IRF6	NM_006147.4	c.-73T>G		5_prime_UTR_variant	2/9	ENST00000367021.8	NP_006138.1
IRF6	NM_001206696.2	c.-112+3906T>G		intron_variant			NP_001193625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF6	ENST00000367021.8	c.-73T>G		splice_region_variant	2/9	1	NM_006147.4	ENSP00000355988.3
ENSG00000289700	ENST00000696133.1	c.-73T>G		splice_region_variant	2/10			ENSP00000512426.1
IRF6	ENST00000367021.8	c.-73T>G		5_prime_UTR_variant	2/9	1	NM_006147.4	ENSP00000355988.3
ENSG00000289700	ENST00000696133.1	c.-73T>G		5_prime_UTR_variant	2/10			ENSP00000512426.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	10
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.50		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.50		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs861019; hg19: chr1-209975386;