chr19-19201687-C-G

Position:

chr19-19201687-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003721.4(RFXANK):c.751C>G(p.Gln251Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0067 in 1,614,100 control chromosomes in the GnomAD database, including 837 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 79 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 758 hom. )

Consequence

RFXANK
NM_003721.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.54

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:

NR2C2AP (HGNC:30763): (nuclear receptor 2C2 associated protein) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NR2C2AP links:

NR2C2AP (HGNC:):

NR2C2AP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014945269).

BP6

Variant 19-19201687-C-G is Benign according to our data. Variant chr19-19201687-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 328648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFXANK	NM_003721.4 linkuse as main transcript	c.751C>G	p.Gln251Glu	missense_variant	10/10	ENST00000303088.9	NP_003712.1	O14593-1A0A024R7M1
NR2C2AP	NM_176880.6 linkuse as main transcript	c.*238G>C		3_prime_UTR_variant	5/5	ENST00000331552.12	NP_795361.1	Q86WQ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RFXANK	ENST00000303088.9 linkuse as main transcript	c.751C>G	p.Gln251Glu	missense_variant	10/10	1	NM_003721.4	ENSP00000305071.2	O14593-1
NR2C2AP	ENST00000331552 linkuse as main transcript	c.*238G>C		3_prime_UTR_variant	5/5	1	NM_176880.6	ENSP00000332823.6	Q86WQ0-1
NR2C2AP	ENST00000420605.7 linkuse as main transcript	c.415-124G>C		intron_variant		2		ENSP00000402756.1	Q86WQ0-2

Frequencies

GnomAD3 genomes

AF:

0.00758

AC:

1153

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.0149

AC:

3728

AN:

251010

Hom.:

294

AF XY:

0.0135

AC XY:

1829

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.000491

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.177

Gnomad SAS exome

AF:

0.00408

Gnomad FIN exome

AF:

0.00450

Gnomad NFE exome

AF:

0.00158

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00661

AC:

9659

AN:

1461800

Hom.:

758

Cov.:

AF XY:

0.00640

AC XY:

4655

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.00394

Gnomad4 FIN exome

AF:

0.00551

Gnomad4 NFE exome

AF:

0.000661

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.00757

AC:

1153

AN:

152300

Hom.:

Cov.:

AF XY:

0.00833

AC XY:

620

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.175

Gnomad4 SAS

AF:

0.00621

Gnomad4 FIN

AF:

0.00499

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00657

Hom.:

Bravo

AF:

0.00780

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0143

AC:

1733

Asia WGS

AF:

0.0770

AC:

268

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000711

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MHC class II deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.093

T;.;T;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.026

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.71

.;T;T;T;.

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;.;M;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.83

N;N;.;N;D

REVEL

Benign

0.050

Sift

Uncertain

0.029

D;D;.;D;.

Sift4G

Uncertain

0.054

T;T;T;T;.

Polyphen

0.0010

B;.;B;.;.

Vest4

0.22

MPC

0.27

ClinPred

0.0094

GERP RS

4.8

Varity_R

0.22

gMVP

0.22

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