rs2654498

chr4-5399599-G-Achr4-5399599-G-C

Variant summary

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

The NM_018401.3(STK32B):c.472+1355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,002 control chromosomes in the GnomAD database, including 39,929 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 0.72 (39929 hom., cov: 31)
• Consequence: STK32B NM_018401.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK32B	NM_018401.3	c.472+1355G>A		intron_variant		ENST00000282908.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK32B	ENST00000282908.10	c.472+1355G>A		intron_variant		1	NM_018401.3	P1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109680 AN: 151884 Hom.: 39902 Cov.: 31

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.722 AC: 109746 AN: 152002 Hom.: 39929 Cov.: 31 AF XY: 0.717 AC XY: 53232 AN XY: 74274

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.750

Alfa AF: 0.739 Hom.: 59286

Bravo AF: 0.716

Asia WGS AF: 0.737 AC: 2560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.3
Dann	Benign	0.78

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: rs2654498; hg19: chr4-5401326;