12-106608780-CTTTTTTTTTTTT-CTTTTTTTTT

Variant names:

• chr12-106608780-CTTT-C
• rs55993073
• NM_213594.3:c.44-5_44-3delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_213594.3(RFX4):​c.44-5_44-3delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000466 in 1,417,594 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00052 (0 hom.)
• Consequence: RFX4 NM_213594.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 2 publications found

Genes affected

RFX4 (HGNC:9985): (regulatory factor X4) This gene is a member of the regulatory factor X gene family, which encodes transcription factors that contain a highly-conserved winged helix DNA binding domain. The protein encoded by this gene is structurally related to regulatory factors X1, X2, X3, and X5. It has been shown to interact with itself as well as with regulatory factors X2 and X3, but it does not interact with regulatory factor X1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

ENSG00000257545 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213594.3. 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
	RFX4	NM_213594.3	MANE Select	c.44-5_44-3delTTT		splice_region intron	N/A	NP_998759.1	Q33E94-1
	RFX4	NM_001206691.2		c.71-5_71-3delTTT		splice_region intron	N/A	NP_001193620.1	Q33E94-2
	LOC100287944	NR_040246.1		n.143-100973_143-100971delAAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX4	ENST00000392842.6	TSL:1 MANE Select	c.44-16_44-14delTTT		intron	N/A	ENSP00000376585.1	Q33E94-1
	RFX4	ENST00000357881.8	TSL:1	c.71-16_71-14delTTT		intron	N/A	ENSP00000350552.4	Q33E94-2
	RFX4	ENST00000536688.5	TSL:1	n.176-16_176-14delTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000278 AC: 4 AN: 143706 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000233

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00179 AC: 219 AN: 122688 AF XY: 0.00187

Gnomad AFR exome AF: 0.00310

Gnomad AMR exome AF: 0.00259

Gnomad ASJ exome AF: 0.00195

Gnomad EAS exome AF: 0.000941

Gnomad FIN exome AF: 0.00145

Gnomad NFE exome AF: 0.00153

Gnomad OTH exome AF: 0.00240

GnomAD4 exome AF: 0.000516 AC: 657 AN: 1273888 Hom.: 0 AF XY: 0.000548 AC XY: 348 AN XY: 634518

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00251 AC: 69 AN: 27474

American (AMR) AF: 0.00175 AC: 50 AN: 28586

Ashkenazi Jewish (ASJ) AF: 0.000817 AC: 18 AN: 22030

East Asian (EAS) AF: 0.000278 AC: 10 AN: 35912

South Asian (SAS) AF: 0.00106 AC: 75 AN: 70540

European-Finnish (FIN) AF: 0.000491 AC: 20 AN: 40698

Middle Eastern (MID) AF: 0.000396 AC: 2 AN: 5056

European-Non Finnish (NFE) AF: 0.000384 AC: 380 AN: 990524

Other (OTH) AF: 0.000622 AC: 33 AN: 53068

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000278 AC: 4 AN: 143706 Hom.: 0 Cov.: 0 AF XY: 0.0000430 AC XY: 3 AN XY: 69742

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000255 AC: 1 AN: 39266

American (AMR) AF: 0.00 AC: 0 AN: 14388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3378

East Asian (EAS) AF: 0.00 AC: 0 AN: 4912

South Asian (SAS) AF: 0.00 AC: 0 AN: 4552

European-Finnish (FIN) AF: 0.000233 AC: 2 AN: 8568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65498

Other (OTH) AF: 0.00 AC: 0 AN: 1964

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0261725), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs55993073; hg19: chr12-107002558;