19-19192464-A-T

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.-240A>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 0.019 in 375,120 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (417 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (51 hom.)
• Consequence: RFXANK NM_003721.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.99

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-19192464-A-T is Benign according to our data. Variant chr19-19192464-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 328637.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFXANK	NM_003721.4	c.-240A>T		5_prime_UTR_variant	1/10	ENST00000303088.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFXANK	ENST00000303088.9	c.-240A>T		5_prime_UTR_variant	1/10	1	NM_003721.4	P1

Frequencies

GnomAD3 genomes AF: 0.0394 AC: 5988 AN: 152038 Hom.: 415 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.00496 AC: 1106 AN: 222964 Hom.: 51 Cov.: 0 AF XY: 0.00435 AC XY: 510 AN XY: 117330

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.00262

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000218

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000370

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.0395 AC: 6008 AN: 152156 Hom.: 417 Cov.: 32 AF XY: 0.0378 AC XY: 2814 AN XY: 74380

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000574

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0224 Hom.: 31

Bravo AF: 0.0442

Asia WGS AF: 0.0110 AC: 38 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	-0.90
Cadd	Benign	0.57
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73922821; hg19: chr19-19303273;