5-137088070-T-C

Variant names:

• chr5-137088070-T-C
• rs2348186
• NM_004598.4:c.475-20241A>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.475-20241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,096 control chromosomes in the GnomAD database, including 13,033 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 0.40 (13033 hom., cov: 32)
• Consequence: SPOCK1 NM_004598.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• 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]

ENSG00000299682 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 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.475-20241A>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.475-20241A>G		intron	N/A	ENSP00000378401.1
	SPOCK1	ENST00000510689.5	TSL:4	c.40-20241A>G		intron	N/A	ENSP00000421677.1
	SPOCK1	ENST00000635347.1	TSL:5	n.448-20241A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60678 AN: 151978 Hom.: 13014 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.399 AC: 60731 AN: 152096 Hom.: 13033 Cov.: 32 AF XY: 0.397 AC XY: 29551 AN XY: 74372

African (AFR) AF: 0.258 AC: 10699 AN: 41498

American (AMR) AF: 0.336 AC: 5127 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3468

East Asian (EAS) AF: 0.398 AC: 2054 AN: 5160

South Asian (SAS) AF: 0.464 AC: 2238 AN: 4824

European-Finnish (FIN) AF: 0.470 AC: 4984 AN: 10594

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32902 AN: 67956

Other (OTH) AF: 0.401 AC: 846 AN: 2112

Alfa AF: 0.416 Hom.: 2422

Bravo AF: 0.379

Asia WGS AF: 0.373 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-0.0090
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: rs2348186; hg19: chr5-136423759;