Variant chr19-13963975-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_002918.5(RFX1):c.2244G>A(p.Leu748Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00641 in 1,539,624 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 43 hom. )

Consequence

RFX1
NM_002918.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.957

Variant links:

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]

RFX1 links:

RFX1 (HGNC:):

RFX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 19-13963975-C-T is Benign according to our data. Variant chr19-13963975-C-T is described in ClinVar as [Benign]. Clinvar id is 718304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.957 with no splicing effect.

BS2

High AC in GnomAd4 at 657 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFX1	NM_002918.5 linkuse as main transcript	c.2244G>A	p.Leu748Leu	synonymous_variant	17/21	ENST00000254325.9	NP_002909.4	P22670

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFX1	ENST00000254325.9 linkuse as main transcript	c.2244G>A	p.Leu748Leu	synonymous_variant	17/21	1	NM_002918.5	ENSP00000254325.3		P22670
RFX1	ENST00000588520.1 linkuse as main transcript	n.81G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00432

AC:

657

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00654

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00453

AC:

652

AN:

143796

Hom.:

AF XY:

0.00427

AC XY:

330

AN XY:

77222

show subpopulations

Gnomad AFR exome

AF:

0.00121

Gnomad AMR exome

AF:

0.00716

Gnomad ASJ exome

AF:

0.000835

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000527

Gnomad FIN exome

AF:

0.000251

Gnomad NFE exome

AF:

0.00737

Gnomad OTH exome

AF:

0.00651

GnomAD4 exome

AF:

0.00664

AC:

9214

AN:

1387250

Hom.:

Cov.:

AF XY:

0.00650

AC XY:

4450

AN XY:

684806

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.00751

Gnomad4 ASJ exome

AF:

0.000915

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000493

Gnomad4 FIN exome

AF:

0.000491

Gnomad4 NFE exome

AF:

0.00775

Gnomad4 OTH exome

AF:

0.00727

GnomAD4 genome

AF:

0.00431

AC:

657

AN:

152374

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

297

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00654

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00489

Hom.:

Bravo

AF:

0.00468

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

8.7

DANN

Benign

0.97

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over