rs17170899

chr5-137040361-C-T

Variant summary

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

The NM_004598.4(SPOCK1):c.589+27354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 152,290 control chromosomes in the GnomAD database, including 160 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 0.043 (160 hom., cov: 33)
• Consequence: SPOCK1 NM_004598.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414

Genes affected

SPOCK1 (HGNC:11251): (SPARC (osteonectin), cwcv and kazal like domains proteoglycan 1) This gene encodes the protein core of a seminal plasma proteoglycan containing chondroitin- and heparan-sulfate chains. The protein's function is unknown, although similarity to thyropin-type cysteine protease-inhibitors suggests its function may be related to protease inhibition. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPOCK1	NM_004598.4	c.589+27354G>A		intron_variant		ENST00000394945.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPOCK1	ENST00000394945.6	c.589+27354G>A		intron_variant		1	NM_004598.4	P1
SPOCK1	ENST00000510689.5	c.154+27354G>A		intron_variant		4
SPOCK1	ENST00000635347.1	n.562+27354G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6563 AN: 152172 Hom.: 162 Cov.: 33

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0447

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0430

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0431 AC: 6566 AN: 152290 Hom.: 160 Cov.: 33 AF XY: 0.0419 AC XY: 3123 AN XY: 74470

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.0580

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.0448

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.0215

Gnomad4 NFE AF: 0.0430

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0367 Hom.: 71

Bravo AF: 0.0469

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.0
Dann	Benign	0.56

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: rs17170899; hg19: chr5-136376050;