3-10117393-CTTTTTTTTTTT-CTTTTTTTTTTTTTT

Variant names:

• chr3-10117393-C-CTTT
• rs756307171
• NM_018462.5:c.118+1592_118+1594dupTTT

Variant summary

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

The NM_018462.5(BRK1):​c.118+1592_118+1594dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 118,606 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 0.00040 (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+1592_118+1594dupTTT		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+1575insTTT		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-1513_114-1512insTTT		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.000396 AC: 47 AN: 118628 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000175

Gnomad ASJ AF: 0.000333

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000277

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000245

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000396 AC: 47 AN: 118606 Hom.: 0 Cov.: 21 AF XY: 0.000355 AC XY: 20 AN XY: 56382

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000941 AC: 29 AN: 30814

American (AMR) AF: 0.000175 AC: 2 AN: 11450

Ashkenazi Jewish (ASJ) AF: 0.000333 AC: 1 AN: 3006

East Asian (EAS) AF: 0.00 AC: 0 AN: 4292

South Asian (SAS) AF: 0.000279 AC: 1 AN: 3580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 222

European-Non Finnish (NFE) AF: 0.000245 AC: 14 AN: 57224

Other (OTH) AF: 0.00 AC: 0 AN: 1594

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000343794), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 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;