chr5-137162804-A-G

Variant names:

• chr5-137162804-A-G
• rs2043478
• NM_004598.4:c.233-22110T>C

Variant summary

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

The NM_004598.4(SPOCK1):​c.233-22110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,060 control chromosomes in the GnomAD database, including 13,205 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 0.41 (13205 hom., cov: 33)
• Consequence: SPOCK1 NM_004598.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 6 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]

ENSG00000293943 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK1	NM_004598.4	c.233-22110T>C		intron_variant	Intron 3 of 10	ENST00000394945.6	NP_004589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOCK1	ENST00000394945.6	c.233-22110T>C		intron_variant	Intron 3 of 10	1	NM_004598.4	ENSP00000378401.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62494 AN: 151942 Hom.: 13193 Cov.: 33

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.411 AC: 62545 AN: 152060 Hom.: 13205 Cov.: 33 AF XY: 0.411 AC XY: 30577 AN XY: 74318

African (AFR) AF: 0.469 AC: 19441 AN: 41474

American (AMR) AF: 0.408 AC: 6239 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3472

East Asian (EAS) AF: 0.606 AC: 3124 AN: 5152

South Asian (SAS) AF: 0.409 AC: 1972 AN: 4818

European-Finnish (FIN) AF: 0.349 AC: 3686 AN: 10576

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25445 AN: 67966

Other (OTH) AF: 0.379 AC: 802 AN: 2116

Alfa AF: 0.388 Hom.: 9876

Bravo AF: 0.419

Asia WGS AF: 0.449 AC: 1561 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.2
DANN	Benign	0.51
PhyloP100		-0.14
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: rs2043478; hg19: chr5-136498493; COSMIC: COSV56442296;