chr1-151341298-A-G

Variant names:

• chr1-151341298-A-G
• rs7552906
• NM_001025603.2:c.*888T>C

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.*888T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,072 control chromosomes in the GnomAD database, including 30,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30209 hom., cov: 31)
  • Exomes 𝑓: 0.50 (9 hom.)
• Consequence: RFX5 NM_001025603.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.216
• Publications: 14 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=-0.88).
• BP6: Variant 1-151341298-A-G is Benign according to our data. Variant chr1-151341298-A-G is described in ClinVar as Benign. ClinVar VariationId is 292600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 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.*888T>C		3_prime_UTR	Exon 11 of 11	NP_001020774.1	P48382-1
	RFX5	NM_000449.4		c.*888T>C		3_prime_UTR	Exon 11 of 11	NP_000440.1	P48382-1
	RFX5	NM_001379412.1		c.*888T>C		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.*888T>C		3_prime_UTR	Exon 11 of 11	ENSP00000389130.2	P48382-1
	RFX5	ENST00000290524.8	TSL:1	c.*888T>C		3_prime_UTR	Exon 11 of 11	ENSP00000290524.4	P48382-1
	RFX5	ENST00000882448.1		c.*888T>C		3_prime_UTR	Exon 10 of 10	ENSP00000552507.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95557 AN: 151878 Hom.: 30201 Cov.: 31

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.500 AC: 38 AN: 76 Hom.: 9 Cov.: 0 AF XY: 0.478 AC XY: 22 AN XY: 46

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.466 AC: 27 AN: 58

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.629 AC: 95616 AN: 151996 Hom.: 30209 Cov.: 31 AF XY: 0.621 AC XY: 46152 AN XY: 74286

African (AFR) AF: 0.623 AC: 25813 AN: 41454

American (AMR) AF: 0.606 AC: 9246 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2073 AN: 3468

East Asian (EAS) AF: 0.643 AC: 3327 AN: 5176

South Asian (SAS) AF: 0.623 AC: 2992 AN: 4804

European-Finnish (FIN) AF: 0.534 AC: 5644 AN: 10560

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44270 AN: 67962

Other (OTH) AF: 0.639 AC: 1348 AN: 2110

Alfa AF: 0.642 Hom.: 39800

Bravo AF: 0.636

Asia WGS AF: 0.662 AC: 2305 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	-0.88
CADD	Benign	3.0
DANN	Benign	0.66
PhyloP100		0.22
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: rs7552906; hg19: chr1-151313774;