chr19-55296218-G-A

Variant names:

• chr19-55296218-G-A
• rs17782355
• NM_032430.2:c.678+1821G>A

Variant summary

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

The NM_032430.2(BRSK1):​c.678+1821G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 151,972 control chromosomes in the GnomAD database, including 89 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 0.029 (89 hom., cov: 31)
• Consequence: BRSK1 NM_032430.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032430.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRSK1	NM_032430.2	MANE Select	c.678+1821G>A		intron	N/A	NP_115806.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRSK1	ENST00000309383.6	TSL:1 MANE Select	c.678+1821G>A		intron	N/A	ENSP00000310649.1
	BRSK1	ENST00000590333.5	TSL:1	c.726+1821G>A		intron	N/A	ENSP00000468190.1
	BRSK1	ENST00000585418.1	TSL:1	c.678+1821G>A		intron	N/A	ENSP00000467357.1

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 4340 AN: 151852 Hom.: 86 Cov.: 31

Gnomad AFR AF: 0.00835

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.0731

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0349

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

GnomAD4 genome AF: 0.0286 AC: 4354 AN: 151972 Hom.: 89 Cov.: 31 AF XY: 0.0287 AC XY: 2132 AN XY: 74266

African (AFR) AF: 0.00835 AC: 346 AN: 41436

American (AMR) AF: 0.0378 AC: 577 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3468

East Asian (EAS) AF: 0.0732 AC: 378 AN: 5162

South Asian (SAS) AF: 0.0677 AC: 325 AN: 4802

European-Finnish (FIN) AF: 0.0159 AC: 168 AN: 10536

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2170 AN: 67990

Other (OTH) AF: 0.0416 AC: 88 AN: 2116

Alfa AF: 0.0144 Hom.: 7

Bravo AF: 0.0284

Asia WGS AF: 0.113 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.54
DANN	Benign	0.40
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism

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: rs17782355; hg19: chr19-55807586;