rs1859345

Positions:

• chr5-137111731-T-C
• chr5-137111731-T-G

Variant summary

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

The NM_004598.4(SPOCK1):​c.474+704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,078 control chromosomes in the GnomAD database, including 5,434 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 0.26 (5434 hom., cov: 31)
• Consequence: SPOCK1 NM_004598.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPOCK1	NM_004598.4	c.474+704A>G		intron_variant		ENST00000394945.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPOCK1	ENST00000394945.6	c.474+704A>G		intron_variant		1	NM_004598.4	P1
SPOCK1	ENST00000510689.5	c.39+704A>G		intron_variant		4
SPOCK1	ENST00000635347.1	n.447+704A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38983 AN: 151960 Hom.: 5427 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.257 AC: 39017 AN: 152078 Hom.: 5434 Cov.: 31 AF XY: 0.254 AC XY: 18861 AN XY: 74348

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.263

Alfa AF: 0.235 Hom.: 1274

Bravo AF: 0.242

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.82

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: rs1859345; hg19: chr5-136447420;