3-10118252-CAAAAAAAAA-CAAAAAAAAAAAAAAAA

Variant names:

• chr3-10118252-C-CAAAAAAA
• rs59622736
• NM_018462.5:c.118+2445_118+2451dupAAAAAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_018462.5(BRK1):​c.118+2445_118+2451dupAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 66,768 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0050 (2 hom., cov: 27)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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+2445_118+2451dupAAAAAAA		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+2434insAAAAAAA		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-654_114-653insAAAAAAA		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.00503 AC: 336 AN: 66754 Hom.: 2 Cov.: 27

Gnomad AFR AF: 0.00231

Gnomad AMI AF: 0.00485

Gnomad AMR AF: 0.00296

Gnomad ASJ AF: 0.00623

Gnomad EAS AF: 0.00100

Gnomad SAS AF: 0.00209

Gnomad FIN AF: 0.00126

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00785

Gnomad OTH AF: 0.00339

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

GnomAD4 genome AF: 0.00503 AC: 336 AN: 66768 Hom.: 2 Cov.: 27 AF XY: 0.00492 AC XY: 154 AN XY: 31302

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00230 AC: 44 AN: 19112

American (AMR) AF: 0.00296 AC: 17 AN: 5734

Ashkenazi Jewish (ASJ) AF: 0.00623 AC: 10 AN: 1604

East Asian (EAS) AF: 0.00101 AC: 2 AN: 1990

South Asian (SAS) AF: 0.00210 AC: 4 AN: 1904

European-Finnish (FIN) AF: 0.00126 AC: 4 AN: 3170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 98

European-Non Finnish (NFE) AF: 0.00785 AC: 250 AN: 31852

Other (OTH) AF: 0.00336 AC: 3 AN: 892

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

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;