3-10119143-C-CA

Position:

• chr3-10119143-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018462.5(BRK1):​c.118+3342dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 66,822 control chromosomes in the GnomAD database, including 1,231 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (1231 hom., cov: 26)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.240

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-10119143-C-CA is Benign according to our data. Variant chr3-10119143-C-CA is described in ClinVar as [Benign]. Clinvar id is 1278998.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRK1	NM_018462.5	c.118+3342dup		intron_variant		ENST00000530758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRK1	ENST00000530758.2	c.118+3342dup		intron_variant		1	NM_018462.5	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 14299 AN: 66794 Hom.: 1230 Cov.: 26

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.0953

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.214 AC: 14298 AN: 66822 Hom.: 1231 Cov.: 26 AF XY: 0.211 AC XY: 6605 AN XY: 31316

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0461

Gnomad4 SAS AF: 0.0936

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.177

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs74416793; hg19: chr3-10160827;