rs1172822

Positions:

• chr19-55308477-C-T

Variant summary

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

The NM_032430.2(BRSK1):​c.2090-162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 146,266 control chromosomes in the GnomAD database, including 8,597 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 0.34 (8597 hom., cov: 26)
• Consequence: BRSK1 NM_032430.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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

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 = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRSK1	NM_032430.2	c.2090-162C>T		intron_variant		ENST00000309383.6	NP_115806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRSK1	ENST00000309383.6	c.2090-162C>T		intron_variant		1	NM_032430.2	ENSP00000310649.1
BRSK1	ENST00000590333.5	c.2138-162C>T		intron_variant		1		ENSP00000468190.1
BRSK1	ENST00000326848.7	c.1175-162C>T		intron_variant		5		ENSP00000320853.7

Frequencies

GnomAD3 genomes AF: 0.338 AC: 49445 AN: 146156 Hom.: 8587 Cov.: 26

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.338 AC: 49477 AN: 146266 Hom.: 8597 Cov.: 26 AF XY: 0.336 AC XY: 23965 AN XY: 71408

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.0795

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.348

Alfa AF: 0.359 Hom.: 17995

Bravo AF: 0.327

Asia WGS AF: 0.292 AC: 1017 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	5.9
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1172822; hg19: chr19-55819845; COSMIC: COSV58594736; COSMIC: COSV58594736;