rs1046391

Positions:

• chr19-5993885-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000635.4(RFX2):​c.*950C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,320 control chromosomes in the GnomAD database, including 963 homozygotes. 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: 𝑓 0.10 (962 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: RFX2 NM_000635.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

Genes affected

RFX2 (HGNC:9983): (regulatory factor X2) 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, X3, X4, and X5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with other RFX family members. This protein can bind to cis elements in the promoter of the IL-5 receptor alpha gene. Two transcript variants encoding different isoforms have been described for this gene, and both variants utilize alternative polyadenylation sites. [provided by RefSeq, Jul 2008]

RANBP3-DT (HGNC:55312): (RANBP3 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFX2	NM_000635.4	c.*950C>A		3_prime_UTR_variant	18/18	ENST00000303657.10
RANBP3-DT	NR_046376.1	n.112+15371G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFX2	ENST00000303657.10	c.*950C>A		3_prime_UTR_variant	18/18	1	NM_000635.4	P3
RFX2	ENST00000359161.7	c.*950C>A		3_prime_UTR_variant	18/18	1		P3
RANBP3-DT	ENST00000587836.1	n.112+15371G>T		intron_variant, non_coding_transcript_variant		3
RANBP3-DT	ENST00000685063.2	n.172+15371G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15988 AN: 152142 Hom.: 966 Cov.: 32

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0424

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.150 AC: 9 AN: 60 Hom.: 1 Cov.: 0 AF XY: 0.235 AC XY: 8 AN XY: 34

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.105 AC: 15980 AN: 152260 Hom.: 962 Cov.: 32 AF XY: 0.106 AC XY: 7868 AN XY: 74434

Gnomad4 AFR AF: 0.0418

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.137

Alfa AF: 0.123 Hom.: 401

Bravo AF: 0.105

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1046391; hg19: chr19-5993896;