19-19192475-C-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.-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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.797

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=-0.81).
• 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_single_submitter, 1 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
RFXANK	NM_003721.4	c.-229C>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.-229C>T		5_prime_UTR_variant	1/10	1	NM_003721.4	P1

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5293 AN: 152156 Hom.: 161 Cov.: 32

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

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

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

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	-0.81
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

Other links and lift over

dbSNP: rs79003009; hg19: chr19-19303284;