NM_001025603.2:c.*244A>G

Variant names:

• chr1-151341942-T-C
• rs2233857
• NM_001025603.2:c.*244A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001025603.2(RFX5):​c.*244A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 696,516 control chromosomes in the GnomAD database, including 537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (113 hom., cov: 32)
  • Exomes 𝑓: 0.034 (424 hom.)
• Consequence: RFX5 NM_001025603.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.512
• Publications: 4 publications found

Genes affected

RFX5 (HGNC:9986): (regulatory factor X5) A lack of MHC-II expression results in a severe immunodeficiency syndrome called MHC-II deficiency, or the bare lymphocyte syndrome (BLS; MIM 209920). At least 4 complementation groups have been identified in B-cell lines established from patients with BLS. The molecular defects in complementation groups B, C, and D all lead to a deficiency in RFX, a nuclear protein complex that binds to the X box of MHC-II promoters. The lack of RFX binding activity in complementation group C results from mutations in the RFX5 gene encoding the 75-kD subunit of RFX (Steimle et al., 1995). RFX5 is the fifth member of the growing family of DNA-binding proteins sharing a novel and highly characteristic DNA-binding domain called the RFX motif. Multiple alternatively spliced transcript variants have been found but the full-length natures of only two have been determined. [provided by RefSeq, Jul 2008]

ENSG00000224645 (HGNC:):

RFX5-AS1 (HGNC:40503): (RFX5 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 1-151341942-T-C is Benign according to our data. Variant chr1-151341942-T-C is described in ClinVar as Benign. ClinVar VariationId is 292606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.03 (4571/152180) while in subpopulation NFE AF = 0.0494 (3358/67994). AF 95% confidence interval is 0.048. There are 113 homozygotes in GnomAd4. There are 2105 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 113 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025603.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX5	NM_001025603.2	MANE Select	c.*244A>G		3_prime_UTR	Exon 11 of 11	NP_001020774.1	P48382-1
	RFX5	NM_000449.4		c.*244A>G		3_prime_UTR	Exon 11 of 11	NP_000440.1	P48382-1
	RFX5	NM_001379412.1		c.*244A>G		3_prime_UTR	Exon 11 of 11	NP_001366341.1	P48382-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX5	ENST00000452671.7	TSL:1 MANE Select	c.*244A>G		3_prime_UTR	Exon 11 of 11	ENSP00000389130.2	P48382-1
	RFX5	ENST00000290524.8	TSL:1	c.*244A>G		3_prime_UTR	Exon 11 of 11	ENSP00000290524.4	P48382-1
	RFX5	ENST00000368870.6	TSL:5	c.*244A>G		3_prime_UTR	Exon 11 of 11	ENSP00000357864.2	P48382-1

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 4571 AN: 152062 Hom.: 113 Cov.: 32

Gnomad AFR AF: 0.00930

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.0413

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0494

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.0344 AC: 18699 AN: 544336 Hom.: 424 Cov.: 4 AF XY: 0.0327 AC XY: 9615 AN XY: 294182

African (AFR) AF: 0.00868 AC: 134 AN: 15430

American (AMR) AF: 0.0104 AC: 352 AN: 33920

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 227 AN: 19280

East Asian (EAS) AF: 0.0000668 AC: 2 AN: 29948

South Asian (SAS) AF: 0.00581 AC: 358 AN: 61604

European-Finnish (FIN) AF: 0.0424 AC: 1934 AN: 45616

Middle Eastern (MID) AF: 0.00613 AC: 23 AN: 3752

European-Non Finnish (NFE) AF: 0.0483 AC: 14747 AN: 305342

Other (OTH) AF: 0.0313 AC: 922 AN: 29444

GnomAD4 genome AF: 0.0300 AC: 4571 AN: 152180 Hom.: 113 Cov.: 32 AF XY: 0.0283 AC XY: 2105 AN XY: 74408

African (AFR) AF: 0.00927 AC: 385 AN: 41534

American (AMR) AF: 0.0127 AC: 194 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3470

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5160

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4830

European-Finnish (FIN) AF: 0.0413 AC: 437 AN: 10590

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0494 AC: 3358 AN: 67994

Other (OTH) AF: 0.0213 AC: 45 AN: 2116

Alfa AF: 0.0352 Hom.: 78

Bravo AF: 0.0275

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	MHC class II deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.4
DANN	Benign	0.85
PhyloP100		-0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2233857; hg19: chr1-151314418;