3-10118252-C-CAAAAAA

Variant names:

• chr3-10118252-C-CAAAAAA
• rs59622736
• NM_018462.5:c.118+2446_118+2451dupAAAAAA

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+2446_118+2451dupAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 66,588 control chromosomes in the GnomAD database, including 150 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.092 (150 hom., cov: 27)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.685
• 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 3-10118252-C-CAAAAAA is Benign according to our data. Variant chr3-10118252-C-CAAAAAA is described in ClinVar as Benign. ClinVar VariationId is 1250650.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 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+2446_118+2451dupAAAAAA		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+2433_118+2434insAAAAAA		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-654_114-653insAAAAAA		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 6105 AN: 66576 Hom.: 150 Cov.: 27

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0757

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.0686

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0797

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

GnomAD4 genome AF: 0.0916 AC: 6102 AN: 66588 Hom.: 150 Cov.: 27 AF XY: 0.0850 AC XY: 2646 AN XY: 31140

African (AFR) AF: 0.0455 AC: 861 AN: 18928

American (AMR) AF: 0.0755 AC: 431 AN: 5710

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 161 AN: 1620

East Asian (EAS) AF: 0.00909 AC: 18 AN: 1980

South Asian (SAS) AF: 0.0515 AC: 97 AN: 1882

European-Finnish (FIN) AF: 0.0423 AC: 133 AN: 3144

Middle Eastern (MID) AF: 0.0435 AC: 4 AN: 92

European-Non Finnish (NFE) AF: 0.133 AC: 4253 AN: 31942

Other (OTH) AF: 0.0790 AC: 70 AN: 886

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		-0.69
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: rs59622736; hg19: chr3-10159936;