rs2233853

Variant names:

• chr1-151343137-G-A
• rs2233853
• NM_001025603.2:c.900C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-151343137-G-A
• chr1-151343137-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001025603.2(RFX5):​c.900C>T​(p.Leu300Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,611,864 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (20 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (19 hom.)
• Consequence: RFX5 NM_001025603.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.96
• Publications: 0 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]

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-151343137-G-A is Benign according to our data. Variant chr1-151343137-G-A is described in ClinVar as Benign. ClinVar VariationId is 471258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.96 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00809 (1232/152336) while in subpopulation AFR AF = 0.028 (1163/41572). AF 95% confidence interval is 0.0266. There are 20 homozygotes in GnomAd4. There are 568 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 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.900C>T	p.Leu300Leu	synonymous	Exon 11 of 11	NP_001020774.1
	RFX5	NM_000449.4		c.900C>T	p.Leu300Leu	synonymous	Exon 11 of 11	NP_000440.1
	RFX5	NM_001379412.1		c.900C>T	p.Leu300Leu	synonymous	Exon 11 of 11	NP_001366341.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX5	ENST00000452671.7	TSL:1 MANE Select	c.900C>T	p.Leu300Leu	synonymous	Exon 11 of 11	ENSP00000389130.2
	RFX5	ENST00000290524.8	TSL:1	c.900C>T	p.Leu300Leu	synonymous	Exon 11 of 11	ENSP00000290524.4
	RFX5	ENST00000368870.6	TSL:5	c.900C>T	p.Leu300Leu	synonymous	Exon 11 of 11	ENSP00000357864.2

Frequencies

GnomAD3 genomes AF: 0.00807 AC: 1228 AN: 152218 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00192 AC: 473 AN: 245866 AF XY: 0.00138

Gnomad AFR exome AF: 0.0279

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000145

Gnomad OTH exome AF: 0.000497

GnomAD4 exome AF: 0.000807 AC: 1178 AN: 1459528 Hom.: 19 Cov.: 33 AF XY: 0.000707 AC XY: 513 AN XY: 726002

African (AFR) AF: 0.0281 AC: 938 AN: 33440

American (AMR) AF: 0.00139 AC: 62 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52470

Middle Eastern (MID) AF: 0.000866 AC: 4 AN: 4618

European-Non Finnish (NFE) AF: 0.0000387 AC: 43 AN: 1111996

Other (OTH) AF: 0.00202 AC: 122 AN: 60256

GnomAD4 genome AF: 0.00809 AC: 1232 AN: 152336 Hom.: 20 Cov.: 32 AF XY: 0.00762 AC XY: 568 AN XY: 74496

African (AFR) AF: 0.0280 AC: 1163 AN: 41572

American (AMR) AF: 0.00333 AC: 51 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00482 Hom.: 3

Bravo AF: 0.00969

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	MHC class II deficiency (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.20
DANN	Benign	0.77
PhyloP100		-2.0
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: rs2233853; hg19: chr1-151315613;