4-5446665-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018401.3(STK32B):c.563-8G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,613,450 control chromosomes in the GnomAD database, including 267 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (150 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (117 hom.)
• Consequence: STK32B NM_018401.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001458
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.17

Genes affected

STK32B (HGNC:14217): (serine/threonine kinase 32B) This gene encodes a serine-threonine protein kinase. Serine-threonine kinases transfer phosphate molecules to the oxygen atoms of serine and threonine. A genomic deletion affecting this gene has been associated with Ellis-van Creveld syndrome, an autosomal recessive skeletal dysplasia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-5446665-G-A is Benign according to our data. Variant chr4-5446665-G-A is described in ClinVar as [Benign]. Clinvar id is 712544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK32B	NM_018401.3	c.563-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000282908.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK32B	ENST00000282908.10	c.563-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018401.3	P1

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3306 AN: 151928 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00573 AC: 1441 AN: 251308 Hom.: 62 AF XY: 0.00462 AC XY: 628 AN XY: 135830

Gnomad AFR exome AF: 0.0762

Gnomad AMR exome AF: 0.00408

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00555

GnomAD4 exome AF: 0.00222 AC: 3238 AN: 1461408 Hom.: 117 Cov.: 30 AF XY: 0.00194 AC XY: 1410 AN XY: 727042

Gnomad4 AFR exome AF: 0.0754

Gnomad4 AMR exome AF: 0.00526

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000136

Gnomad4 OTH exome AF: 0.00485

GnomAD4 genome AF: 0.0218 AC: 3316 AN: 152042 Hom.: 150 Cov.: 32 AF XY: 0.0213 AC XY: 1583 AN XY: 74290

Gnomad4 AFR AF: 0.0747

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00662 Hom.: 14

Bravo AF: 0.0264

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 01, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.97
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.026
SpliceAI score (max)		0.010		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: rs11930847; hg19: chr4-5448392; COSMIC: COSV99285355;