rs623244

Variant names:

• chr3-33402794-T-A
• rs623244
• NM_014517.5:c.1031+7A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-33402794-T-A
• chr3-33402794-T-C
• chr3-33402794-T-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014517.5(UBP1):​c.1031+7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,546,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: UBP1 NM_014517.5 splice_region, intron
• Scores: Splicing: ADA: 0.0004768
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 14 publications found

Genes affected

UBP1 (HGNC:12507): (upstream binding protein 1) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of viral transcription and positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FBXL2 (HGNC:13598): (F-box and leucine rich repeat protein 2) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains 12 tandem leucine-rich repeats. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS2: High AC in GnomAdExome4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBP1	NM_014517.5	c.1031+7A>T		splice_region_variant, intron_variant	Intron 9 of 15	ENST00000283629.8	NP_055332.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBP1	ENST00000283629.8	c.1031+7A>T		splice_region_variant, intron_variant	Intron 9 of 15	1	NM_014517.5	ENSP00000283629.3

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151808 Hom.: 0 Cov.: 31

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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000650 AC: 12 AN: 184548 AF XY: 0.0000906

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000282

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000232

GnomAD4 exome AF: 0.0000308 AC: 43 AN: 1394668 Hom.: 0 Cov.: 28 AF XY: 0.0000392 AC XY: 27 AN XY: 689372

African (AFR) AF: 0.00 AC: 0 AN: 30454

American (AMR) AF: 0.0000322 AC: 1 AN: 31034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22720

East Asian (EAS) AF: 0.000317 AC: 12 AN: 37864

South Asian (SAS) AF: 0.000340 AC: 26 AN: 76376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51100

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5490

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082130

Other (OTH) AF: 0.0000348 AC: 2 AN: 57500

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151808 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74126

African (AFR) AF: 0.00 AC: 0 AN: 41264

American (AMR) AF: 0.00 AC: 0 AN: 15250

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 46710

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.6
DANN	Benign	0.74
PhyloP100		-0.080
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00048
dbscSNV1_RF	Benign	0.040
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: rs623244; hg19: chr3-33444286;