3-10118252-CAAAAAAAAA-CAAAAAAAAAAAAA

Variant names:

• chr3-10118252-C-CAAAA
• rs59622736
• NM_018462.5:c.118+2448_118+2451dupAAAA

Variant summary

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

The NM_018462.5(BRK1):​c.118+2448_118+2451dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 67,480 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0031 (1 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+2448_118+2451dupAAAA		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+2434insAAAA		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-654_114-653insAAAA		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.00314 AC: 212 AN: 67468 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000315

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000154

Gnomad OTH AF: 0.00338

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

GnomAD4 genome AF: 0.00314 AC: 212 AN: 67480 Hom.: 1 Cov.: 27 AF XY: 0.00291 AC XY: 92 AN XY: 31588

African (AFR) AF: 0.0103 AC: 197 AN: 19186

American (AMR) AF: 0.00104 AC: 6 AN: 5770

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: 0.000315 AC: 1 AN: 3172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 98

European-Non Finnish (NFE) AF: 0.000154 AC: 5 AN: 32406

Other (OTH) AF: 0.00335 AC: 3 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;