Variant 3-10115684-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018462.5(BRK1):c.-18C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,605,720 control chromosomes in the GnomAD database, including 14,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2579 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12399 hom. )

Consequence

BRK1
NM_018462.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0800

Variant links:

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]

BRK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 3-10115684-C-T is Benign according to our data. Variant chr3-10115684-C-T is described in ClinVar as [Benign]. Clinvar id is 1178768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRK1	NM_018462.5 linkuse as main transcript	c.-18C>T		5_prime_UTR_variant	1/3	ENST00000530758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRK1	ENST00000530758.2 linkuse as main transcript	c.-18C>T		5_prime_UTR_variant	1/3	1	NM_018462.5	P1	Q8WUW1-1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24833

AN:

152090

Hom.:

2576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.0876

Gnomad EAS

AF:

0.0320

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.0827

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.135

GnomAD3 exomes

AF:

0.129

AC:

31938

AN:

246932

Hom.:

2556

AF XY:

0.128

AC XY:

17206

AN XY:

134424

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.0936

Gnomad EAS exome

AF:

0.0329

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.0871

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.125

AC:

181612

AN:

1453512

Hom.:

12399

Cov.:

AF XY:

0.125

AC XY:

90272

AN XY:

723534

show subpopulations

Gnomad4 AFR exome

AF:

0.303

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.0938

Gnomad4 EAS exome

AF:

0.0267

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.0902

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.163

AC:

24858

AN:

152208

Hom.:

2579

Cov.:

AF XY:

0.160

AC XY:

11921

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.0876

Gnomad4 EAS

AF:

0.0319

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.0827

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.134

Hom.:

370

Bravo

AF:

0.173

Asia WGS

AF:

0.0920

AC:

321

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.5

DANN

Benign

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over