NM_018462.5:c.118+3342delA

Variant names:

• chr3-10119143-CA-C
• rs74416793
• NM_018462.5:c.118+3342delA

Variant summary

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

The NM_018462.5(BRK1):​c.118+3342delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 67,440 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 0.011 (2 hom., cov: 26)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: 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+3342delA		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+3325delA		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.178+174delA		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 760 AN: 67412 Hom.: 2 Cov.: 26

Gnomad AFR AF: 0.00498

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00640

Gnomad ASJ AF: 0.00858

Gnomad EAS AF: 0.00963

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0157

Gnomad OTH AF: 0.00966

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

GnomAD4 genome AF: 0.0113 AC: 761 AN: 67440 Hom.: 2 Cov.: 26 AF XY: 0.0101 AC XY: 319 AN XY: 31534

African (AFR) AF: 0.00502 AC: 104 AN: 20734

American (AMR) AF: 0.00639 AC: 37 AN: 5792

Ashkenazi Jewish (ASJ) AF: 0.00858 AC: 14 AN: 1632

East Asian (EAS) AF: 0.00962 AC: 17 AN: 1768

South Asian (SAS) AF: 0.0129 AC: 24 AN: 1856

European-Finnish (FIN) AF: 0.0218 AC: 61 AN: 2798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 92

European-Non Finnish (NFE) AF: 0.0157 AC: 496 AN: 31546

Other (OTH) AF: 0.00955 AC: 8 AN: 838

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24
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: rs74416793; hg19: chr3-10160827;