chr3-10120199-C-CT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018462.5(BRK1):​c.118+4393dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 143,624 control chromosomes in the GnomAD database, including 2,415 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2415 hom., cov: 27)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-10120199-C-CT is Benign according to our data. Variant chr3-10120199-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1268599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

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+4393dupT		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+4380_118+4381insT		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.178+1229_178+1230insT		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 24021 AN: 143570 Hom.: 2417 Cov.: 27

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0873

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.167 AC: 24037 AN: 143624 Hom.: 2415 Cov.: 27 AF XY: 0.165 AC XY: 11519 AN XY: 69732

African (AFR) AF: 0.296 AC: 11661 AN: 39376

American (AMR) AF: 0.135 AC: 1926 AN: 14226

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 301 AN: 3342

East Asian (EAS) AF: 0.0328 AC: 162 AN: 4934

South Asian (SAS) AF: 0.162 AC: 729 AN: 4492

European-Finnish (FIN) AF: 0.0873 AC: 791 AN: 9056

Middle Eastern (MID) AF: 0.0971 AC: 27 AN: 278

European-Non Finnish (NFE) AF: 0.123 AC: 8030 AN: 65098

Other (OTH) AF: 0.141 AC: 273 AN: 1942

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

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;