Variant NM_001282116.2:c.2011+9C>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001282116.2(RFX3):c.2011+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00844 in 1,602,248 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0087 ( 70 hom. )

Consequence

RFX3
NM_001282116.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.278

Variant links:

Genes affected

RFX3 (HGNC:9984): (regulatory factor X3) 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, X4, and X5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with other RFX family members. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2013]

RFX3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 9-3228838-G-A is Benign according to our data. Variant chr9-3228838-G-A is described in ClinVar as [Benign]. Clinvar id is 778032.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00621 (945/152076) while in subpopulation NFE AF= 0.01 (682/67996). AF 95% confidence interval is 0.00941. There are 2 homozygotes in gnomad4. There are 457 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 945 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFX3	NM_001282116.2 link	c.2011+9C>T		intron_variant	Intron 16 of 16	ENST00000617270.5	NP_001269045.1	P48380-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFX3	ENST00000617270.5 link	c.2011+9C>T		intron_variant	Intron 16 of 16	2	NM_001282116.2	ENSP00000482598.1		P48380-1
RFX3	ENST00000382004.7 link	c.2011+9C>T		intron_variant	Intron 17 of 17	1		ENSP00000371434.3		P48380-1

Frequencies

GnomAD3 genomes

AF:

0.00622

AC:

945

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00217

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00596

AC:

1441

AN:

241582

Hom.:

AF XY:

0.00610

AC XY:

797

AN XY:

130680

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.0000563

Gnomad SAS exome

AF:

0.000428

Gnomad FIN exome

AF:

0.00975

Gnomad NFE exome

AF:

0.00923

Gnomad OTH exome

AF:

0.00683

GnomAD4 exome

AF:

0.00867

AC:

12577

AN:

1450172

Hom.:

Cov.:

AF XY:

0.00850

AC XY:

6135

AN XY:

721482

show subpopulations

Gnomad4 AFR exome

AF:

0.000976

Gnomad4 AMR exome

AF:

0.00109

Gnomad4 ASJ exome

AF:

0.00993

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000595

Gnomad4 FIN exome

AF:

0.00938

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.00771

GnomAD4 genome

AF:

0.00621

AC:

945

AN:

152076

Hom.:

Cov.:

AF XY:

0.00615

AC XY:

457

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00174

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00844

Hom.:

Bravo

AF:

0.00516

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

RFX3-related disorder

Benign:1

Jun 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.56

DANN

Benign

0.65

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