rs1888523

Variant names:

• chr21-43105109-G-A
• rs1888523
• ENST00000459639.5:c.-882C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000459639.5(U2AF1):​c.-882C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 15)
  • Failed GnomAD Quality Control
• Consequence: U2AF1 ENST00000459639.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 9 publications found

Genes affected

U2AF1 (HGNC:12453): (U2 small nuclear RNA auxiliary factor 1) This gene belongs to the splicing factor SR family of genes. U2 auxiliary factor, comprising a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the small subunit which plays a critical role in both constitutive and enhancer-dependent RNA splicing by directly mediating interactions between the large subunit and proteins bound to the enhancers. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000459639.5. 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
	U2AF1	NM_006758.3	MANE Select	c.45-707C>T		intron	N/A	NP_006749.1	Q01081-1
	U2AF1	NM_001025203.1		c.45-707C>T		intron	N/A	NP_001020374.1	Q01081-2
	U2AF1	NM_001025204.2		c.-242-707C>T		intron	N/A	NP_001020375.1	Q01081-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	U2AF1	ENST00000459639.5	TSL:1	c.-882C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000418705.1	Q01081-4
	U2AF1	ENST00000459639.5	TSL:1	c.-882C>T		5_prime_UTR	Exon 1 of 7	ENSP00000418705.1	Q01081-4
	U2AF1	ENST00000291552.9	TSL:1 MANE Select	c.45-707C>T		intron	N/A	ENSP00000291552.4	Q01081-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 108782 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 108782 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 52786

African (AFR) AF: 0.00 AC: 0 AN: 24598

American (AMR) AF: 0.00 AC: 0 AN: 10178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2900

East Asian (EAS) AF: 0.00 AC: 0 AN: 5030

South Asian (SAS) AF: 0.00 AC: 0 AN: 3890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51936

Other (OTH) AF: 0.00 AC: 0 AN: 1500

Alfa AF: 0.450 Hom.: 34546

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.42
PhyloP100		-1.2
PromoterAI		0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1888523;

hg19: chr21-44525219;