3-141126743-G-A

Variant names:

• chr3-141126743-G-A
• rs1007118
• NM_080862.3:c.695-20399G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080862.3. 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
	SPSB4	NM_080862.3	MANE Select	c.695-20399G>A		intron	N/A	NP_543138.1	Q96A44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB4	ENST00000310546.3	TSL:1 MANE Select	c.695-20399G>A		intron	N/A	ENSP00000311609.2	Q96A44
	SPSB4	ENST00000887577.1		c.695-20399G>A		intron	N/A	ENSP00000557636.1
	SPSB4	ENST00000931037.1		c.695-20399G>A		intron	N/A	ENSP00000601096.1

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

African (AFR) AF: 0.00346 AC: 144 AN: 41562

American (AMR) AF: 0.00790 AC: 121 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00767 AC: 37 AN: 4826

European-Finnish (FIN) AF: 0.00546 AC: 58 AN: 10626

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0190 AC: 1289 AN: 68014

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.0127 Hom.: 6

Bravo AF: 0.0116

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		0.015
Mutation Taster		=100/0	polymorphism

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: rs1007118; hg19: chr3-140845585;