4-5399599-G-A

Variant names:

• chr4-5399599-G-A
• rs2654498
• NM_018401.3:c.472+1355G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018401.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK32B	NM_018401.3	MANE Select	c.472+1355G>A		intron	N/A	NP_060871.1
	STK32B	NM_001345969.2		c.472+1355G>A		intron	N/A	NP_001332898.1
	STK32B	NM_001306082.2		c.331+1355G>A		intron	N/A	NP_001293011.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK32B	ENST00000282908.10	TSL:1 MANE Select	c.472+1355G>A		intron	N/A	ENSP00000282908.5
	STK32B	ENST00000510398.1	TSL:1	c.331+1355G>A		intron	N/A	ENSP00000420984.1
	STK32B	ENST00000512018.5	TSL:1	n.*426+1355G>A		intron	N/A	ENSP00000422820.1

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

African (AFR) AF: 0.725 AC: 30079 AN: 41464

American (AMR) AF: 0.615 AC: 9403 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2764 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3772 AN: 5138

South Asian (SAS) AF: 0.727 AC: 3496 AN: 4810

European-Finnish (FIN) AF: 0.706 AC: 7459 AN: 10572

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50405 AN: 67948

Other (OTH) AF: 0.750 AC: 1580 AN: 2108

Alfa AF: 0.738 Hom.: 90960

Bravo AF: 0.716

Asia WGS AF: 0.737 AC: 2560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.78
PhyloP100		0.15
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: rs2654498; hg19: chr4-5401326;