NM_004598.4:c.186+11227G>A

Variant names:

• chr5-137487146-C-T
• rs1919515
• NM_004598.4:c.186+11227G>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+11227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,764 control chromosomes in the GnomAD database, including 10,366 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 0.37 (10366 hom., cov: 31)
• Consequence: SPOCK1 NM_004598.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK1	NM_004598.4	c.186+11227G>A		intron_variant	Intron 2 of 10	ENST00000394945.6	NP_004589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOCK1	ENST00000394945.6	c.186+11227G>A		intron_variant	Intron 2 of 10	1	NM_004598.4	ENSP00000378401.1
SPOCK1	ENST00000505690.1	c.186+11227G>A		intron_variant	Intron 1 of 3	2		ENSP00000424517.1
SPOCK1	ENST00000510689.5	c.-250+12033G>A		intron_variant	Intron 1 of 5	4		ENSP00000421677.1
SPOCK1	ENST00000503916.1	n.251+18493G>A		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55814 AN: 151646 Hom.: 10370 Cov.: 31

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.368 AC: 55803 AN: 151764 Hom.: 10366 Cov.: 31 AF XY: 0.369 AC XY: 27391 AN XY: 74132

African (AFR) AF: 0.334 AC: 13822 AN: 41326

American (AMR) AF: 0.341 AC: 5202 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1446 AN: 3468

East Asian (EAS) AF: 0.463 AC: 2387 AN: 5160

South Asian (SAS) AF: 0.330 AC: 1584 AN: 4794

European-Finnish (FIN) AF: 0.414 AC: 4348 AN: 10494

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25706 AN: 67962

Other (OTH) AF: 0.385 AC: 809 AN: 2104

Alfa AF: 0.373 Hom.: 5417

Bravo AF: 0.369

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		-0.12
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: rs1919515; hg19: chr5-136822835;