rs1551562

Positions:

• chr19-55303513-A-G

Variant summary

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

The NM_032430.2(BRSK1):​c.1126+105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,481,246 control chromosomes in the GnomAD database, including 36,483 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 0.19 (2976 hom., cov: 32)
  • Exomes 𝑓: 0.22 (33507 hom.)
• Consequence: BRSK1 NM_032430.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622

Genes affected

BRSK1 (HGNC:18994): (BR serine/threonine kinase 1) Enables magnesium ion binding activity; protein serine/threonine kinase activity; and tau-protein kinase activity. Involved in mitotic G2 DNA damage checkpoint signaling and protein phosphorylation. Acts upstream of or within G2/M transition of mitotic cell cycle; peptidyl-serine phosphorylation; and response to UV. Located in cell junction; cytoplasm; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BRSK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRSK1	NM_032430.2	c.1126+105A>G		intron_variant		ENST00000309383.6	NP_115806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRSK1	ENST00000309383.6	c.1126+105A>G		intron_variant		1	NM_032430.2	ENSP00000310649.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28341 AN: 151994 Hom.: 2975 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0607

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.221 AC: 293293 AN: 1329134 Hom.: 33507 Cov.: 19 AF XY: 0.223 AC XY: 148018 AN XY: 665100

Gnomad4 AFR exome AF: 0.0993

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0516

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.186 AC: 28344 AN: 152112 Hom.: 2976 Cov.: 32 AF XY: 0.186 AC XY: 13791 AN XY: 74342

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.0607

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.202

Alfa AF: 0.221 Hom.: 5764

Bravo AF: 0.181

Asia WGS AF: 0.166 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.53

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: rs1551562; hg19: chr19-55814881;