NM_018462.5:c.118+2447_118+2451dupAAAAA

Variant names:

• chr3-10118252-C-CAAAAA
• rs59622736
• NM_018462.5:c.118+2447_118+2451dupAAAAA

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+2447_118+2451dupAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 66,932 control chromosomes in the GnomAD database, including 486 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (486 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-CAAAAA is Benign according to our data. Variant chr3-10118252-C-CAAAAA is described in ClinVar as Benign. ClinVar VariationId is 1251563.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 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+2447_118+2451dupAAAAA		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+2434insAAAAA		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-654_114-653insAAAAA		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 7587 AN: 66912 Hom.: 487 Cov.: 27

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0357

Gnomad AMR AF: 0.0905

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.00664

Gnomad MID AF: 0.0377

Gnomad NFE AF: 0.0384

Gnomad OTH AF: 0.0966

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

GnomAD4 genome AF: 0.113 AC: 7589 AN: 66932 Hom.: 486 Cov.: 27 AF XY: 0.114 AC XY: 3557 AN XY: 31320

African (AFR) AF: 0.282 AC: 5311 AN: 18832

American (AMR) AF: 0.0906 AC: 517 AN: 5704

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 65 AN: 1622

East Asian (EAS) AF: 0.0485 AC: 96 AN: 1980

South Asian (SAS) AF: 0.124 AC: 234 AN: 1884

European-Finnish (FIN) AF: 0.00664 AC: 21 AN: 3164

Middle Eastern (MID) AF: 0.0313 AC: 3 AN: 96

European-Non Finnish (NFE) AF: 0.0384 AC: 1241 AN: 32342

Other (OTH) AF: 0.0968 AC: 86 AN: 888

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 (auto)

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;