rs73922821

Variant names:

• chr19-19192464-A-T
• rs73922821
• ENST00000477565.3:c.-347T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• MHC class II deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RFXANK	NM_003721.4	c.-240A>T		5_prime_UTR_variant	Exon 1 of 10	ENST00000303088.9	NP_003712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFXANK	ENST00000303088.9	c.-240A>T		5_prime_UTR_variant	Exon 1 of 10	1	NM_003721.4	ENSP00000305071.2

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

African (AFR) AF: 0.119 AC: 767 AN: 6456

American (AMR) AF: 0.0109 AC: 90 AN: 8224

Ashkenazi Jewish (ASJ) AF: 0.00262 AC: 19 AN: 7240

East Asian (EAS) AF: 0.00 AC: 0 AN: 14144

South Asian (SAS) AF: 0.000218 AC: 5 AN: 22962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14250

Middle Eastern (MID) AF: 0.0107 AC: 11 AN: 1030

European-Non Finnish (NFE) AF: 0.000370 AC: 50 AN: 135314

Other (OTH) AF: 0.0123 AC: 164 AN: 13344

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

African (AFR) AF: 0.136 AC: 5656 AN: 41496

American (AMR) AF: 0.0162 AC: 247 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000574 AC: 39 AN: 67996

Other (OTH) AF: 0.0241 AC: 51 AN: 2112

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.72
PhyloP100		-2.0
PromoterAI		-0.018	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73922821; hg19: chr19-19303273;