19-19192475-C-T

Variant summary

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

The NM_003721.4(RFXANK):​c.-229C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 357,878 control chromosomes in the GnomAD database, including 419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 162 hom., cov: 32)
Exomes 𝑓: 0.038 ( 257 hom. )

Consequence

RFXANK
NM_003721.4 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.797
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]
BORCS8 (HGNC:37247): (BLOC-1 related complex subunit 8) Involved in heart development. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

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 (BayesDel_noAF=-0.81).
BP6
Variant 19-19192475-C-T is Benign according to our data. Variant chr19-19192475-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 328638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RFXANKNM_003721.4 linkuse as main transcriptc.-229C>T 5_prime_UTR_variant 1/10 ENST00000303088.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RFXANKENST00000303088.9 linkuse as main transcriptc.-229C>T 5_prime_UTR_variant 1/101 NM_003721.4 P1O14593-1

Frequencies

GnomAD3 genomes
AF:
0.0348
AC:
5293
AN:
152156
Hom.:
161
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00646
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0764
Gnomad ASJ
AF:
0.0493
Gnomad EAS
AF:
0.130
Gnomad SAS
AF:
0.0547
Gnomad FIN
AF:
0.0335
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.0342
Gnomad OTH
AF:
0.0306
GnomAD4 exome
AF:
0.0384
AC:
7893
AN:
205604
Hom.:
257
Cov.:
0
AF XY:
0.0387
AC XY:
4185
AN XY:
108142
show subpopulations
Gnomad4 AFR exome
AF:
0.00513
Gnomad4 AMR exome
AF:
0.0799
Gnomad4 ASJ exome
AF:
0.0422
Gnomad4 EAS exome
AF:
0.109
Gnomad4 SAS exome
AF:
0.0421
Gnomad4 FIN exome
AF:
0.0327
Gnomad4 NFE exome
AF:
0.0301
Gnomad4 OTH exome
AF:
0.0386
GnomAD4 genome
AF:
0.0348
AC:
5297
AN:
152274
Hom.:
162
Cov.:
32
AF XY:
0.0360
AC XY:
2682
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00645
Gnomad4 AMR
AF:
0.0765
Gnomad4 ASJ
AF:
0.0493
Gnomad4 EAS
AF:
0.130
Gnomad4 SAS
AF:
0.0551
Gnomad4 FIN
AF:
0.0335
Gnomad4 NFE
AF:
0.0342
Gnomad4 OTH
AF:
0.0307
Alfa
AF:
0.0124
Hom.:
1
Bravo
AF:
0.0362
Asia WGS
AF:
0.0890
AC:
307
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

MHC class II deficiency Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
2.2
DANN
Benign
0.89

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.

Other links and lift over

dbSNP: rs79003009; hg19: chr19-19303284; API