19-13965494-G-C

Position:

• chr19-13965494-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002918.5(RFX1):​c.2166C>G​(p.Leu722Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000725 in 1,614,022 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (11 hom.)
• Consequence: RFX1 NM_002918.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 19-13965494-G-C is Benign according to our data. Variant chr19-13965494-G-C is described in ClinVar as [Benign]. Clinvar id is 726865.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.24 with no splicing effect.
• BS2: High AC in GnomAd4 at 89 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFX1	NM_002918.5	c.2166C>G	p.Leu722Leu	synonymous_variant	16/21	ENST00000254325.9	NP_002909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFX1	ENST00000254325.9	c.2166C>G	p.Leu722Leu	synonymous_variant	16/21	1	NM_002918.5	ENSP00000254325.3

Frequencies

GnomAD3 genomes AF: 0.000578 AC: 88 AN: 152182 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00770

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00171 AC: 429 AN: 251268 Hom.: 2 AF XY: 0.00141 AC XY: 191 AN XY: 135836

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00853

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00533

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000740 AC: 1081 AN: 1461722 Hom.: 11 Cov.: 33 AF XY: 0.000696 AC XY: 506 AN XY: 727156

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00763

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0158

Gnomad4 SAS exome AF: 0.000719

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.000397

GnomAD4 genome AF: 0.000584 AC: 89 AN: 152300 Hom.: 1 Cov.: 32 AF XY: 0.000645 AC XY: 48 AN XY: 74476

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00772

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000444 Hom.: 0

Bravo AF: 0.000774

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.6
DANN	Benign	0.79

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: rs149654538; hg19: chr19-14076306;