rs12511127

Positions:

• chr4-5140485-A-G
• chr4-5140485-A-T

Variant summary

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

The NM_018401.3(STK32B):​c.108+525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,988 control chromosomes in the GnomAD database, including 12,870 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 0.37 (12870 hom., cov: 32)
• Consequence: STK32B NM_018401.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK32B	NM_018401.3	c.108+525A>G		intron_variant		ENST00000282908.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK32B	ENST00000282908.10	c.108+525A>G		intron_variant		1	NM_018401.3	P1
STK32B	ENST00000510398.1	c.-34+525A>G		intron_variant		1
STK32B	ENST00000512018.5	c.*62+179A>G		intron_variant, NMD_transcript_variant		1
STK32B	ENST00000512636.5	c.-34+525A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56318 AN: 151870 Hom.: 12869 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.371 AC: 56314 AN: 151988 Hom.: 12870 Cov.: 32 AF XY: 0.367 AC XY: 27227 AN XY: 74266

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.401

Alfa AF: 0.487 Hom.: 25723

Bravo AF: 0.351

Asia WGS AF: 0.390 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.31

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: rs12511127; hg19: chr4-5142212;