rs72997200

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_003721.4(RFXANK):c.213C>T(p.Thr71Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,612,860 control chromosomes in the GnomAD database, including 3,386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.046 ( 218 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3168 hom. )

Consequence

RFXANK
NM_003721.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -1.50

Variant links:

Genes affected

RFXANK (HGNC:9987): (regulatory factor X associated ankyrin containing protein) Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune system. The protein encoded by this gene, along with regulatory factor X-associated protein and regulatory factor-5, forms a complex that binds to the X box motif of certain MHC class II gene promoters and activates their transcription. Once bound to the promoter, this complex associates with the non-DNA-binding factor MHC class II transactivator, which controls the cell type specificity and inducibility of MHC class II gene expression. This protein contains ankyrin repeats involved in protein-protein interactions. Mutations in this gene have been linked to bare lymphocyte syndrome type II, complementation group B. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2013]

RFXANK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-19196988-C-T is Benign according to our data. Variant chr19-19196988-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 328642.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1}.

BP7

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFXANK	NM_003721.4 link	c.213C>T	p.Thr71Thr	synonymous_variant	Exon 4 of 10	ENST00000303088.9	NP_003712.1	O14593-1A0A024R7M1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFXANK	ENST00000303088.9 link	c.213C>T	p.Thr71Thr	synonymous_variant	Exon 4 of 10	1	NM_003721.4	ENSP00000305071.2		O14593-1

Frequencies

GnomAD3 genomes

AF:

0.0460

AC:

7001

AN:

152156

Hom.:

218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0462

Gnomad ASJ

AF:

0.0871

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0470

Gnomad FIN

AF:

0.0525

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0674

Gnomad OTH

AF:

0.0545

GnomAD3 exomes

AF:

0.0525

AC:

13109

AN:

249892

Hom.:

428

AF XY:

0.0551

AC XY:

7453

AN XY:

135178

show subpopulations

Gnomad AFR exome

AF:

0.00950

Gnomad AMR exome

AF:

0.0319

Gnomad ASJ exome

AF:

0.0888

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0519

Gnomad FIN exome

AF:

0.0592

Gnomad NFE exome

AF:

0.0686

Gnomad OTH exome

AF:

0.0613

GnomAD4 exome

AF:

0.0628

AC:

91729

AN:

1460586

Hom.:

3168

Cov.:

AF XY:

0.0635

AC XY:

46151

AN XY:

726598

show subpopulations

Gnomad4 AFR exome

AF:

0.00989

Gnomad4 AMR exome

AF:

0.0334

Gnomad4 ASJ exome

AF:

0.0877

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0532

Gnomad4 FIN exome

AF:

0.0583

Gnomad4 NFE exome

AF:

0.0681

Gnomad4 OTH exome

AF:

0.0634

GnomAD4 genome

AF:

0.0460

AC:

6999

AN:

152274

Hom.:

218

Cov.:

AF XY:

0.0449

AC XY:

3342

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0112

Gnomad4 AMR

AF:

0.0462

Gnomad4 ASJ

AF:

0.0871

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0466

Gnomad4 FIN

AF:

0.0525

Gnomad4 NFE

AF:

0.0674

Gnomad4 OTH

AF:

0.0540

Alfa

AF:

0.0617

Hom.:

110

Bravo

AF:

0.0428

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0722

EpiControl

AF:

0.0694

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

MHC class II deficiency

Uncertain:1Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.12

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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