4-5051893-C-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_018401.3(STK32B):c.30C>A(p.Pro10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,599,922 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (35 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (27 hom.)
• Consequence: STK32B NM_018401.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.76

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 4-5051893-C-A is Benign according to our data. Variant chr4-5051893-C-A is described in ClinVar as [Benign]. Clinvar id is 778139.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.76 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1757/152350) while in subpopulation AFR AF= 0.0389 (1616/41584). AF 95% confidence interval is 0.0373. There are 35 homozygotes in gnomad4. There are 819 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK32B	NM_018401.3	c.30C>A	p.Pro10=	synonymous_variant	1/12	ENST00000282908.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK32B	ENST00000282908.10	c.30C>A	p.Pro10=	synonymous_variant	1/12	1	NM_018401.3	P1
STK32B	ENST00000512018.5	c.30C>A	p.Pro10=	synonymous_variant, NMD_transcript_variant	1/13	1

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1754 AN: 152232 Hom.: 35 Cov.: 33

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00292 AC: 654 AN: 223850 Hom.: 8 AF XY: 0.00245 AC XY: 297 AN XY: 121124

Gnomad AFR exome AF: 0.0390

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000607

Gnomad SAS exome AF: 0.0000729

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000340

Gnomad OTH exome AF: 0.00255

GnomAD4 exome AF: 0.00137 AC: 1988 AN: 1447572 Hom.: 27 Cov.: 30 AF XY: 0.00126 AC XY: 907 AN XY: 718900

Gnomad4 AFR exome AF: 0.0416

Gnomad4 AMR exome AF: 0.00268

Gnomad4 ASJ exome AF: 0.0000387

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000479

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.000274

Gnomad4 OTH exome AF: 0.00278

GnomAD4 genome AF: 0.0115 AC: 1757 AN: 152350 Hom.: 35 Cov.: 33 AF XY: 0.0110 AC XY: 819 AN XY: 74506

Gnomad4 AFR AF: 0.0389

Gnomad4 AMR AF: 0.00581

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00363 Hom.: 6

Bravo AF: 0.0128

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

Aug 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	2.2
Dann	Benign	0.91

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: rs77843312; hg19: chr4-5053620;