chr3-10120199-C-CT

Position:

• chr3-10120199-C-CT

Variant summary

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

The NM_018462.5(BRK1):​c.118+4393dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 143,624 control chromosomes in the GnomAD database, including 2,415 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2415 hom., cov: 27)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.631

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 3-10120199-C-CT is Benign according to our data. Variant chr3-10120199-C-CT is described in ClinVar as [Benign]. Clinvar id is 1268599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRK1	NM_018462.5	c.118+4393dup		intron_variant		ENST00000530758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRK1	ENST00000530758.2	c.118+4393dup		intron_variant		1	NM_018462.5	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 24021 AN: 143570 Hom.: 2417 Cov.: 27

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0873

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.167 AC: 24037 AN: 143624 Hom.: 2415 Cov.: 27 AF XY: 0.165 AC XY: 11519 AN XY: 69732

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0901

Gnomad4 EAS AF: 0.0328

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0873

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.141

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 19, 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: rs546079992; hg19: chr3-10161883;