NM_018462.5:c.118+1593_118+1594delTT

Variant names:

• chr3-10117393-CTT-C
• rs756307171
• NM_018462.5:c.118+1593_118+1594delTT

Variant summary

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

The NM_018462.5(BRK1):​c.118+1593_118+1594delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 118,586 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 0.00045 (0 hom., cov: 21)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• 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+1593_118+1594delTT		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+1575_118+1576delTT		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-1512_114-1511delTT		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.000438 AC: 52 AN: 118608 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000780

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000875

Gnomad ASJ AF: 0.000332

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000888

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000349

Gnomad OTH AF: 0.000631

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

GnomAD4 genome AF: 0.000447 AC: 53 AN: 118586 Hom.: 0 Cov.: 21 AF XY: 0.000461 AC XY: 26 AN XY: 56376

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

African (AFR) AF: 0.000811 AC: 25 AN: 30820

American (AMR) AF: 0.0000874 AC: 1 AN: 11446

Ashkenazi Jewish (ASJ) AF: 0.000332 AC: 1 AN: 3010

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 3578

European-Finnish (FIN) AF: 0.000888 AC: 5 AN: 5630

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

European-Non Finnish (NFE) AF: 0.000350 AC: 20 AN: 57212

Other (OTH) AF: 0.000627 AC: 1 AN: 1594

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000931877), 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		-0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs756307171; hg19: chr3-10159077;