rs16851055

Positions:

• chr3-141080371-G-A
• chr3-141080371-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080862.3(SPSB4):​c.694+13573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,242 control chromosomes in the GnomAD database, including 6,062 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 0.25 (6061 hom., cov: 33)
  • Exomes 𝑓: 0.36 (1 hom.)
• Consequence: SPSB4 NM_080862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPSB4	NM_080862.3	c.694+13573G>A		intron_variant		ENST00000310546.3	NP_543138.1
SPSB4	XM_017007509.3	c.*74G>A		3_prime_UTR_variant	3/3		XP_016862998.1
SPSB4	XR_924215.4	n.1575G>A		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPSB4	ENST00000310546.3	c.694+13573G>A		intron_variant		1	NM_080862.3	ENSP00000311609	P1
SPSB4	ENST00000508126.1	c.161+13573G>A		intron_variant		2		ENSP00000422034
SPSB4	ENST00000507895.1	n.220G>A		non_coding_transcript_exon_variant	2/3	5
SPSB4	ENST00000508828.1	n.535G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38533 AN: 152102 Hom.: 6055 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.364 AC: 8 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.389 AC XY: 7 AN XY: 18

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.350

GnomAD4 genome AF: 0.253 AC: 38568 AN: 152220 Hom.: 6061 Cov.: 33 AF XY: 0.246 AC XY: 18322 AN XY: 74426

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.240

Alfa AF: 0.204 Hom.: 4634

Bravo AF: 0.266

Asia WGS AF: 0.185 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.62

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: rs16851055; hg19: chr3-140799213;