dbSNP rs6442154: BRK1:c.*806T>C (chr3-10127101-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018462.5(BRK1):c.*806T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,352 control chromosomes in the GnomAD database, including 2,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2577 hom., cov: 33)

Exomes 𝑓: 0.065 ( 0 hom. )

Consequence

BRK1
NM_018462.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.324

Publications

17 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-10127101-T-C is Benign according to our data. Variant chr3-10127101-T-C is described in ClinVar as Benign. ClinVar VariationId is 1263802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRK1	NM_018462.5 link	c.*806T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000530758.2	NP_060932.2	Q8WUW1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRK1	ENST00000530758.2 link	c.*806T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_018462.5	ENSP00000432472.1		Q8WUW1-1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24862

AN:

152096

Hom.:

2574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.0877

Gnomad EAS

AF:

0.0319

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.0834

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.134

GnomAD4 exome

AF:

0.0652

AC:

AN:

138

Hom.:

Cov.:

AF XY:

0.0795

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0682

AC:

AN:

132

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.164

AC:

24887

AN:

152214

Hom.:

2577

Cov.:

AF XY:

0.160

AC XY:

11930

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.291

AC:

12085

AN:

41518

American (AMR)

AF:

0.129

AC:

1971

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0877

AC:

304

AN:

3468

East Asian (EAS)

AF:

0.0318

AC:

165

AN:

5194

South Asian (SAS)

AF:

0.155

AC:

747

AN:

4826

European-Finnish (FIN)

AF:

0.0834

AC:

885

AN:

10616

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8281

AN:

68004

Other (OTH)

AF:

0.135

AC:

285

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1011

2022

3032

4043

5054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.135

Hom.:

2065

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.9

(source)

DANN

Benign

0.82

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over