rs1551562

Variant names:

• chr19-55303513-A-G
• rs1551562
• NM_032430.2:c.1126+105A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BRSK1	NM_032430.2	c.1126+105A>G		intron_variant	Intron 11 of 18	ENST00000309383.6	NP_115806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRSK1	ENST00000309383.6	c.1126+105A>G		intron_variant	Intron 11 of 18	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

African (AFR) AF: 0.0993 AC: 2995 AN: 30152

American (AMR) AF: 0.169 AC: 6800 AN: 40274

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 6104 AN: 24424

East Asian (EAS) AF: 0.0516 AC: 2005 AN: 38860

South Asian (SAS) AF: 0.243 AC: 19902 AN: 81960

European-Finnish (FIN) AF: 0.217 AC: 11281 AN: 51916

Middle Eastern (MID) AF: 0.195 AC: 1053 AN: 5390

European-Non Finnish (NFE) AF: 0.231 AC: 231185 AN: 1000430

Other (OTH) AF: 0.215 AC: 11968 AN: 55728

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

African (AFR) AF: 0.105 AC: 4354 AN: 41518

American (AMR) AF: 0.203 AC: 3098 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3470

East Asian (EAS) AF: 0.0607 AC: 314 AN: 5176

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4818

European-Finnish (FIN) AF: 0.213 AC: 2255 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15595 AN: 67970

Other (OTH) AF: 0.202 AC: 427 AN: 2114

Alfa AF: 0.217 Hom.: 8273

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
PhyloP100		0.62
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: rs1551562; hg19: chr19-55814881;