4-5438497-G-T

Variant names:

• chr4-5438497-G-T
• rs6827240
• NM_018401.3:c.563-8176G>T

Variant summary

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

The NM_018401.3(STK32B):​c.563-8176G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,122 control chromosomes in the GnomAD database, including 13,336 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 (13336 hom., cov: 32)
• Consequence: STK32B NM_018401.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK32B	NM_018401.3	c.563-8176G>T		intron_variant	Intron 6 of 11	ENST00000282908.10	NP_060871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK32B	ENST00000282908.10	c.563-8176G>T		intron_variant	Intron 6 of 11	1	NM_018401.3	ENSP00000282908.5

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62049 AN: 152004 Hom.: 13335 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0919

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.408 AC: 62075 AN: 152122 Hom.: 13336 Cov.: 32 AF XY: 0.402 AC XY: 29920 AN XY: 74346

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.0921

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.382

Alfa AF: 0.428 Hom.: 28865

Bravo AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.60

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: rs6827240; hg19: chr4-5440224;