1-151341903-T-C

Variant names:

• chr1-151341903-T-C
• rs1752387
• NM_001025603.2:c.*283A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001025603.2(RFX5):​c.*283A>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 0.764 in 602,896 control chromosomes in the GnomAD database, including 177,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46969 hom., cov: 31)
  • Exomes 𝑓: 0.76 (130177 hom.)
• Consequence: RFX5 NM_001025603.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.79
• Publications: 18 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=-0.83).
• BP6: Variant 1-151341903-T-C is Benign according to our data. Variant chr1-151341903-T-C is described in ClinVar as Benign. ClinVar VariationId is 292605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

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.*283A>G		3_prime_UTR	Exon 11 of 11	NP_001020774.1	P48382-1
	RFX5	NM_000449.4		c.*283A>G		3_prime_UTR	Exon 11 of 11	NP_000440.1	P48382-1
	RFX5	NM_001379412.1		c.*283A>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.*283A>G		3_prime_UTR	Exon 11 of 11	ENSP00000389130.2	P48382-1
	RFX5	ENST00000290524.8	TSL:1	c.*283A>G		3_prime_UTR	Exon 11 of 11	ENSP00000290524.4	P48382-1
	RFX5	ENST00000368870.6	TSL:5	c.*283A>G		3_prime_UTR	Exon 11 of 11	ENSP00000357864.2	P48382-1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119050 AN: 151922 Hom.: 46919 Cov.: 31

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.816

GnomAD4 exome AF: 0.757 AC: 341414 AN: 450856 Hom.: 130177 Cov.: 3 AF XY: 0.757 AC XY: 185442 AN XY: 244830

African (AFR) AF: 0.842 AC: 10433 AN: 12384

American (AMR) AF: 0.757 AC: 18025 AN: 23820

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 13029 AN: 15316

East Asian (EAS) AF: 0.648 AC: 15734 AN: 24272

South Asian (SAS) AF: 0.735 AC: 40618 AN: 55286

European-Finnish (FIN) AF: 0.657 AC: 24484 AN: 37254

Middle Eastern (MID) AF: 0.842 AC: 2052 AN: 2438

European-Non Finnish (NFE) AF: 0.774 AC: 197880 AN: 255624

Other (OTH) AF: 0.783 AC: 19159 AN: 24462

GnomAD4 genome AF: 0.784 AC: 119158 AN: 152040 Hom.: 46969 Cov.: 31 AF XY: 0.777 AC XY: 57704 AN XY: 74300

African (AFR) AF: 0.839 AC: 34817 AN: 41478

American (AMR) AF: 0.774 AC: 11820 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2963 AN: 3472

East Asian (EAS) AF: 0.697 AC: 3583 AN: 5138

South Asian (SAS) AF: 0.722 AC: 3479 AN: 4816

European-Finnish (FIN) AF: 0.652 AC: 6874 AN: 10548

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52868 AN: 67994

Other (OTH) AF: 0.818 AC: 1725 AN: 2110

Alfa AF: 0.783 Hom.: 53836

Bravo AF: 0.798

Asia WGS AF: 0.761 AC: 2650 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	-0.83
CADD	Benign	0.95
DANN	Benign	0.78
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs1752387; hg19: chr1-151314379; COSMIC: COSV51841510; COSMIC: COSV51841510;