chr5-137105393-T-C

Position:

• chr5-137105393-T-C

Variant summary

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

The NM_004598.4(SPOCK1):​c.474+7042A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,100 control chromosomes in the GnomAD database, including 5,390 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 0.25 (5390 hom., cov: 32)
• Consequence: SPOCK1 NM_004598.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOCK1	NM_004598.4	c.474+7042A>G		intron_variant		ENST00000394945.6	NP_004589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPOCK1	ENST00000394945.6	c.474+7042A>G		intron_variant		1	NM_004598.4	ENSP00000378401	P1
SPOCK1	ENST00000510689.5	c.39+7042A>G		intron_variant		4		ENSP00000421677
SPOCK1	ENST00000635347.1	n.447+7042A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38308 AN: 151982 Hom.: 5385 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.252 AC: 38333 AN: 152100 Hom.: 5390 Cov.: 32 AF XY: 0.250 AC XY: 18614 AN XY: 74368

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.256

Alfa AF: 0.288 Hom.: 1443

Bravo AF: 0.236

Asia WGS AF: 0.224 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.73

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: rs13357391; hg19: chr5-136441082;