3-10120199-CTTT-CTT

Variant names:

• chr3-10120199-CT-C
• rs546079992
• NM_018462.5:c.118+4393delT

Variant summary

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

The NM_018462.5(BRK1):​c.118+4393delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 27)
  • Failed GnomAD Quality Control
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• 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+4393delT		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+4381delT		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.178+1230delT		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 230 AN: 143230 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000407

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00127

Gnomad ASJ AF: 0.000601

Gnomad EAS AF: 0.000202

Gnomad SAS AF: 0.000221

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.000520

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00161 AC: 230 AN: 143284 Hom.: 0 Cov.: 27 AF XY: 0.00183 AC XY: 127 AN XY: 69536

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

African (AFR) AF: 0.000406 AC: 16 AN: 39378

American (AMR) AF: 0.00127 AC: 18 AN: 14212

Ashkenazi Jewish (ASJ) AF: 0.000601 AC: 2 AN: 3330

East Asian (EAS) AF: 0.000203 AC: 1 AN: 4932

South Asian (SAS) AF: 0.00 AC: 0 AN: 4498

European-Finnish (FIN) AF: 0.0107 AC: 95 AN: 8910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00148 AC: 96 AN: 64930

Other (OTH) AF: 0.00103 AC: 2 AN: 1936

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs546079992; hg19: chr3-10161883;