rs1007118

Positions:

• chr3-141126743-G-A
• chr3-141126743-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_080862.3(SPSB4):​c.695-20399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 152,312 control chromosomes in the GnomAD database, including 21 homozygotes. 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 0.011 (21 hom., cov: 33)
• Consequence: SPSB4 NM_080862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

Genes affected

SPSB4 (HGNC:30630): (splA/ryanodine receptor domain and SOCS box containing 4) Enables ubiquitin ligase-substrate adaptor activity. Involved in cellular protein metabolic process; positive regulation of protein polyubiquitination; and regulation of circadian rhythm. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SPSB4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0114 (1735/152312) while in subpopulation NFE AF= 0.019 (1289/68014). AF 95% confidence interval is 0.0181. There are 21 homozygotes in gnomad4. There are 748 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPSB4	NM_080862.3	c.695-20399G>A		intron_variant		ENST00000310546.3	NP_543138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPSB4	ENST00000310546.3	c.695-20399G>A		intron_variant		1	NM_080862.3	ENSP00000311609.2
SPSB4	ENST00000508126.1	c.161-5446G>A		intron_variant		2		ENSP00000422034.1
SPSB4	ENST00000507895.1	n.258-20399G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1735 AN: 152194 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.00347

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.00791

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00546

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0114 AC: 1735 AN: 152312 Hom.: 21 Cov.: 33 AF XY: 0.0100 AC XY: 748 AN XY: 74494

Gnomad4 AFR AF: 0.00346

Gnomad4 AMR AF: 0.00790

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.00546

Gnomad4 NFE AF: 0.0190

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0129 Hom.: 2

Bravo AF: 0.0116

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1007118; hg19: chr3-140845585;