3-10118252-CAAAAAAAAA-CAAAAAAAAAAA

Variant names:

• chr3-10118252-C-CAA
• rs59622736
• NM_018462.5:c.118+2450_118+2451dupAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018462.5(BRK1):​c.118+2450_118+2451dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 67,454 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00021 (0 hom., cov: 27)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685
• Publications: 0 publications found

Genes affected

BRK1 (HGNC:23057): (BRICK1 subunit of SCAR/WAVE actin nucleating complex) Enables identical protein binding activity. Contributes to small GTPase binding activity. Involved in Rac protein signal transduction and positive regulation of cellular component organization. Located in extracellular exosome. Part of SCAR complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018462.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRK1	NM_018462.5	MANE Select	c.118+2450_118+2451dupAA		intron	N/A	NP_060932.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRK1	ENST00000530758.2	TSL:1 MANE Select	c.118+2433_118+2434insAA		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-654_114-653insAA		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.000193 AC: 13 AN: 67442 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000316

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000216

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000208 AC: 14 AN: 67454 Hom.: 0 Cov.: 27 AF XY: 0.000253 AC XY: 8 AN XY: 31574

African (AFR) AF: 0.000313 AC: 6 AN: 19182

American (AMR) AF: 0.00 AC: 0 AN: 5768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1628

East Asian (EAS) AF: 0.00 AC: 0 AN: 1990

South Asian (SAS) AF: 0.00 AC: 0 AN: 1914

European-Finnish (FIN) AF: 0.000316 AC: 1 AN: 3168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 96

European-Non Finnish (NFE) AF: 0.000216 AC: 7 AN: 32392

Other (OTH) AF: 0.00 AC: 0 AN: 896

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs59622736; hg19: chr3-10159936;