3-10118252-CAAAAAAAAA-CAAAAAAAAAA

Variant names:

• chr3-10118252-C-CA
• rs59622736
• NM_018462.5:c.118+2451dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018462.5(BRK1):​c.118+2451dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 67,190 control chromosomes in the GnomAD database, including 10 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.012 (10 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0124 (836/67190) while in subpopulation NFE AF = 0.0175 (565/32212). AF 95% confidence interval is 0.0163. There are 10 homozygotes in GnomAd4. There are 387 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 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+2451dupA		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+2434insA		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-654_114-653insA		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 836 AN: 67178 Hom.: 10 Cov.: 27

Gnomad AFR AF: 0.00596

Gnomad AMI AF: 0.00721

Gnomad AMR AF: 0.00974

Gnomad ASJ AF: 0.000616

Gnomad EAS AF: 0.0126

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.00680

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

GnomAD4 genome AF: 0.0124 AC: 836 AN: 67190 Hom.: 10 Cov.: 27 AF XY: 0.0123 AC XY: 387 AN XY: 31456

African (AFR) AF: 0.00595 AC: 114 AN: 19146

American (AMR) AF: 0.00974 AC: 56 AN: 5752

Ashkenazi Jewish (ASJ) AF: 0.000616 AC: 1 AN: 1624

East Asian (EAS) AF: 0.0127 AC: 25 AN: 1976

South Asian (SAS) AF: 0.0105 AC: 20 AN: 1910

European-Finnish (FIN) AF: 0.0145 AC: 46 AN: 3166

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

European-Non Finnish (NFE) AF: 0.0175 AC: 565 AN: 32212

Other (OTH) AF: 0.00674 AC: 6 AN: 890

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

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: rs59622736; hg19: chr3-10159936;