NM_032430.2:c.318-519T>C

Variant names:

• chr19-55288961-T-C
• rs12611091
• NM_032430.2:c.318-519T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032430.2(BRSK1):​c.318-519T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,968 control chromosomes in the GnomAD database, including 19,141 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 0.50 (19141 hom., cov: 31)
• Consequence: BRSK1 NM_032430.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988
• Publications: 18 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRSK1	NM_032430.2	c.318-519T>C		intron_variant	Intron 3 of 18	ENST00000309383.6	NP_115806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRSK1	ENST00000309383.6	c.318-519T>C		intron_variant	Intron 3 of 18	1	NM_032430.2	ENSP00000310649.1
BRSK1	ENST00000590333.5	c.366-519T>C		intron_variant	Intron 5 of 20	1		ENSP00000468190.1
BRSK1	ENST00000585418.1	c.318-519T>C		intron_variant	Intron 3 of 9	1		ENSP00000467357.1
BRSK1	ENST00000592539.6	n.*63-519T>C		intron_variant	Intron 4 of 6	5		ENSP00000466755.2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75403 AN: 151850 Hom.: 19125 Cov.: 31

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.496 AC: 75451 AN: 151968 Hom.: 19141 Cov.: 31 AF XY: 0.499 AC XY: 37050 AN XY: 74266

African (AFR) AF: 0.475 AC: 19668 AN: 41444

American (AMR) AF: 0.546 AC: 8336 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3470

East Asian (EAS) AF: 0.771 AC: 3976 AN: 5160

South Asian (SAS) AF: 0.439 AC: 2115 AN: 4822

European-Finnish (FIN) AF: 0.490 AC: 5170 AN: 10544

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33364 AN: 67958

Other (OTH) AF: 0.468 AC: 987 AN: 2108

Alfa AF: 0.491 Hom.: 71291

Bravo AF: 0.505

Asia WGS AF: 0.531 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.99
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: rs12611091; hg19: chr19-55800329;