19-13975701-G-C

Position:

• chr19-13975701-G-C

Variant summary

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

The NM_002918.5(RFX1):​c.929+2291C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,152 control chromosomes in the GnomAD database, including 20,087 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 0.49 (20087 hom., cov: 33)
• Consequence: RFX1 NM_002918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.05

Genes affected

RFX1 (HGNC:9982): (regulatory factor X1) This gene encodes a member of the regulatory factor X (RFX) family of transcription factors, which are characterized by a winged-helix DNA-binding domain. The encoded transcription factor contains an N-terminal activation domain and a C-terminal repression domain, and may activate or repress target gene expression depending on cellular context. This transcription factor has been shown to regulate a wide variety of genes involved in immunity and cancer, including the MHC class II genes and genes that may be involved in cancer progression. This gene exhibits altered expression in glioblastoma and the autoimmune disease systemic lupus erythematosis (SLE). [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFX1	NM_002918.5	c.929+2291C>G		intron_variant		ENST00000254325.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFX1	ENST00000254325.9	c.929+2291C>G		intron_variant		1	NM_002918.5	P1
RFX1	ENST00000589239.5	n.1201+2291C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74698 AN: 152034 Hom.: 20037 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.457

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.492 AC: 74807 AN: 152152 Hom.: 20087 Cov.: 33 AF XY: 0.488 AC XY: 36299 AN XY: 74366

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.460

Alfa AF: 0.445 Hom.: 2040

Bravo AF: 0.504

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0020
DANN	Benign	0.43

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: rs11085876; hg19: chr19-14086513;