NM_018462.5:c.118+3342dupA

Variant names:

• chr3-10119143-C-CA
• rs74416793
• NM_018462.5:c.118+3342dupA

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+3342dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 66,822 control chromosomes in the GnomAD database, including 1,231 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (1231 hom., cov: 26)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.240
• 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 3-10119143-C-CA is Benign according to our data. Variant chr3-10119143-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1278998.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 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+3342dupA		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+3324_118+3325insA		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.178+173_178+174insA		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 14299 AN: 66794 Hom.: 1230 Cov.: 26

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.0953

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.214 AC: 14298 AN: 66822 Hom.: 1231 Cov.: 26 AF XY: 0.211 AC XY: 6605 AN XY: 31316

African (AFR) AF: 0.334 AC: 6886 AN: 20622

American (AMR) AF: 0.147 AC: 848 AN: 5764

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 193 AN: 1600

East Asian (EAS) AF: 0.0461 AC: 81 AN: 1758

South Asian (SAS) AF: 0.0936 AC: 173 AN: 1848

European-Finnish (FIN) AF: 0.105 AC: 296 AN: 2806

Middle Eastern (MID) AF: 0.167 AC: 15 AN: 90

European-Non Finnish (NFE) AF: 0.179 AC: 5562 AN: 31122

Other (OTH) AF: 0.177 AC: 147 AN: 830

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		0.24
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: rs74416793; hg19: chr3-10160827;