rs1229718

Variant names:

• chr5-137408103-C-T
• rs1229718
• NM_004598.4:c.186+90270G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004598.4(SPOCK1):​c.186+90270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,116 control chromosomes in the GnomAD database, including 6,888 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 0.28 (6888 hom., cov: 32)
• Consequence: SPOCK1 NM_004598.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004598.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOCK1	NM_004598.4	MANE Select	c.186+90270G>A		intron	N/A	NP_004589.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOCK1	ENST00000394945.6	TSL:1 MANE Select	c.186+90270G>A		intron	N/A	ENSP00000378401.1
	SPOCK1	ENST00000505690.1	TSL:2	c.186+90270G>A		intron	N/A	ENSP00000424517.1
	SPOCK1	ENST00000510689.5	TSL:4	c.-250+91076G>A		intron	N/A	ENSP00000421677.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42149 AN: 151998 Hom.: 6896 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.277 AC: 42136 AN: 152116 Hom.: 6888 Cov.: 32 AF XY: 0.278 AC XY: 20655 AN XY: 74350

African (AFR) AF: 0.0929 AC: 3858 AN: 41542

American (AMR) AF: 0.276 AC: 4212 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1293 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1304 AN: 5170

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4822

European-Finnish (FIN) AF: 0.354 AC: 3732 AN: 10550

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.369 AC: 25104 AN: 67976

Other (OTH) AF: 0.307 AC: 648 AN: 2114

Alfa AF: 0.318 Hom.: 14246

Bravo AF: 0.263

Asia WGS AF: 0.213 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.61
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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: rs1229718; hg19: chr5-136743792;