19-19192376-G-A

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.-328G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 579,840 control chromosomes in the GnomAD database, including 6,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1243 hom., cov: 32)
  • Exomes 𝑓: 0.14 (4965 hom.)
• Consequence: RFXANK NM_003721.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.335

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=-0.83).
• BP6: Variant 19-19192376-G-A is Benign according to our data. Variant chr19-19192376-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 328635.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFXANK	NM_003721.4	c.-328G>A		5_prime_UTR_variant	1/10	ENST00000303088.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFXANK	ENST00000303088.9	c.-328G>A		5_prime_UTR_variant	1/10	1	NM_003721.4	P1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16849 AN: 152094 Hom.: 1245 Cov.: 32

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.140 AC: 59680 AN: 427628 Hom.: 4965 Cov.: 3 AF XY: 0.141 AC XY: 31614 AN XY: 224616

Gnomad4 AFR exome AF: 0.0268

Gnomad4 AMR exome AF: 0.0711

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.000306

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.111 AC: 16844 AN: 152212 Hom.: 1243 Cov.: 32 AF XY: 0.111 AC XY: 8254 AN XY: 74410

Gnomad4 AFR AF: 0.0280

Gnomad4 AMR AF: 0.0849

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.106

Alfa AF: 0.109 Hom.: 364

Bravo AF: 0.0966

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.0
Dann	Benign	0.68

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: rs62135502; hg19: chr19-19303185;