19-19192993-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003721.4(RFXANK):c.-116T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,234 control chromosomes in the GnomAD database, including 2,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2790 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: RFXANK NM_003721.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-19192993-T-C is Benign according to our data. Variant chr19-19192993-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 328639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFXANK	NM_003721.4	c.-116T>C		5_prime_UTR_variant	2/10	ENST00000303088.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFXANK	ENST00000303088.9	c.-116T>C		5_prime_UTR_variant	2/10	1	NM_003721.4	P1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26548 AN: 152006 Hom.: 2775 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.145 AC: 16 AN: 110 Hom.: 1 Cov.: 0 AF XY: 0.125 AC XY: 10 AN XY: 80

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.357

Gnomad4 NFE exome AF: 0.0976

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.175 AC: 26596 AN: 152124 Hom.: 2790 Cov.: 32 AF XY: 0.175 AC XY: 13008 AN XY: 74370

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.0695

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.158

Alfa AF: 0.139 Hom.: 2158

Bravo AF: 0.188

Asia WGS AF: 0.285 AC: 989 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MHC class II deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.2
Dann	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1050483; hg19: chr19-19303802;