3-10117393-CTTTTTTTTTTT-CTTTTTTTTTTTTTTTT

Variant names:

• chr3-10117393-C-CTTTTT
• rs756307171
• NM_018462.5:c.118+1590_118+1594dupTTTTT

Variant summary

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

The NM_018462.5(BRK1):​c.118+1590_118+1594dupTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 118,646 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 0.00013 (0 hom., cov: 21)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931
• 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+1590_118+1594dupTTTTT		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+1574_118+1575insTTTTT		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-1513_114-1512insTTTTT		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.000135 AC: 16 AN: 118646 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000487

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000874

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000135 AC: 16 AN: 118646 Hom.: 0 Cov.: 21 AF XY: 0.000142 AC XY: 8 AN XY: 56402

African (AFR) AF: 0.000487 AC: 15 AN: 30776

American (AMR) AF: 0.0000874 AC: 1 AN: 11438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3010

East Asian (EAS) AF: 0.00 AC: 0 AN: 4310

South Asian (SAS) AF: 0.00 AC: 0 AN: 3604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57248

Other (OTH) AF: 0.00 AC: 0 AN: 1586

Alfa AF: 0.000218 Hom.: 70

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs756307171; hg19: chr3-10159077;