NM_004598.4:c.474+704A>G

Variant names:

• chr5-137111731-T-C
• rs1859345
• NM_004598.4:c.474+704A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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]

ENSG00000299682 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.474+704A>G		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.474+704A>G		intron	N/A	ENSP00000378401.1
	SPOCK1	ENST00000510689.5	TSL:4	c.39+704A>G		intron	N/A	ENSP00000421677.1
	SPOCK1	ENST00000635347.1	TSL:5	n.447+704A>G		intron	N/A

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

African (AFR) AF: 0.151 AC: 6245 AN: 41494

American (AMR) AF: 0.219 AC: 3348 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3466

East Asian (EAS) AF: 0.164 AC: 849 AN: 5176

South Asian (SAS) AF: 0.273 AC: 1316 AN: 4812

European-Finnish (FIN) AF: 0.341 AC: 3608 AN: 10568

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21892 AN: 67974

Other (OTH) AF: 0.263 AC: 556 AN: 2112

Alfa AF: 0.235 Hom.: 1274

Bravo AF: 0.242

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.82
PhyloP100		-0.59
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: rs1859345; hg19: chr5-136447420;