NM_018462.5:c.118+3341_118+3342dupAA

Variant names:

• chr3-10119143-C-CAA
• rs74416793
• NM_018462.5:c.118+3341_118+3342dupAA

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+3341_118+3342dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 67,304 control chromosomes in the GnomAD database, including 78 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.047 (78 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-CAA is Benign according to our data. Variant chr3-10119143-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 1249200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0602 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+3341_118+3342dupAA		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+3325insAA		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.178+173_178+174insAA		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 3196 AN: 67276 Hom.: 78 Cov.: 26

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.0421

Gnomad AMR AF: 0.0659

Gnomad ASJ AF: 0.0417

Gnomad EAS AF: 0.000569

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.00428

Gnomad MID AF: 0.0294

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0533

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

GnomAD4 genome AF: 0.0475 AC: 3194 AN: 67304 Hom.: 78 Cov.: 26 AF XY: 0.0473 AC XY: 1488 AN XY: 31472

African (AFR) AF: 0.0602 AC: 1245 AN: 20688

American (AMR) AF: 0.0656 AC: 379 AN: 5774

Ashkenazi Jewish (ASJ) AF: 0.0417 AC: 68 AN: 1630

East Asian (EAS) AF: 0.000569 AC: 1 AN: 1758

South Asian (SAS) AF: 0.0609 AC: 113 AN: 1854

European-Finnish (FIN) AF: 0.00428 AC: 12 AN: 2804

Middle Eastern (MID) AF: 0.0109 AC: 1 AN: 92

European-Non Finnish (NFE) AF: 0.0418 AC: 1315 AN: 31488

Other (OTH) AF: 0.0526 AC: 44 AN: 836

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs74416793; hg19: chr3-10160827;