rs1172822

Variant names:

• chr19-55308477-C-T
• rs1172822
• NM_032430.2:c.2090-162C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 42 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 = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRSK1	NM_032430.2	c.2090-162C>T		intron_variant	Intron 17 of 18	ENST00000309383.6	NP_115806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRSK1	ENST00000309383.6	c.2090-162C>T		intron_variant	Intron 17 of 18	1	NM_032430.2	ENSP00000310649.1
BRSK1	ENST00000590333.5	c.2138-162C>T		intron_variant	Intron 19 of 20	1		ENSP00000468190.1
BRSK1	ENST00000326848.7	c.1175-162C>T		intron_variant	Intron 9 of 10	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

African (AFR) AF: 0.295 AC: 11105 AN: 37606

American (AMR) AF: 0.375 AC: 5585 AN: 14886

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1295 AN: 3424

East Asian (EAS) AF: 0.0795 AC: 407 AN: 5118

South Asian (SAS) AF: 0.485 AC: 2326 AN: 4796

European-Finnish (FIN) AF: 0.299 AC: 3034 AN: 10150

Middle Eastern (MID) AF: 0.315 AC: 90 AN: 286

European-Non Finnish (NFE) AF: 0.368 AC: 24683 AN: 67094

Other (OTH) AF: 0.348 AC: 700 AN: 2012

Alfa AF: 0.351 Hom.: 40025

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
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1172822; hg19: chr19-55819845; COSMIC: COSV58594736; COSMIC: COSV58594736;