chr3-141073523-A-G

Position:

• chr3-141073523-A-G

Variant summary

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

The NM_080862.3(SPSB4):​c.694+6725A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,208 control chromosomes in the GnomAD database, including 3,994 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 0.13 (3994 hom., cov: 32)
• Consequence: SPSB4 NM_080862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPSB4	NM_080862.3	c.694+6725A>G		intron_variant		ENST00000310546.3
SPSB4	XM_017007509.3	c.694+6725A>G		intron_variant
SPSB4	XR_924215.4	n.1493+6725A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPSB4	ENST00000310546.3	c.694+6725A>G		intron_variant		1	NM_080862.3	P1
SPSB4	ENST00000508126.1	c.161+6725A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19359 AN: 152090 Hom.: 3966 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00403

Gnomad OTH AF: 0.0871

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

GnomAD4 genome AF: 0.128 AC: 19438 AN: 152208 Hom.: 3994 Cov.: 32 AF XY: 0.124 AC XY: 9216 AN XY: 74428

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.00401

Gnomad4 OTH AF: 0.0862

Alfa AF: 0.0201 Hom.: 757

Bravo AF: 0.144

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.8
DANN	Benign	0.54

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: rs16851040; hg19: chr3-140792365;