rs6442154

Positions:

• chr3-10127101-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.324

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 -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 id 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/exons	MANE	UniProt
BRK1	NM_018462.5	c.*806T>C		3_prime_UTR_variant	3/3	ENST00000530758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRK1	ENST00000530758.2	c.*806T>C		3_prime_UTR_variant	3/3	1	NM_018462.5	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24862 AN: 152096 Hom.: 2574 Cov.: 33

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: 9 AN: 138 Hom.: 0 Cov.: 0 AF XY: 0.0795 AC XY: 7 AN XY: 88

Gnomad4 FIN exome AF: 0.0682

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.164 AC: 24887 AN: 152214 Hom.: 2577 Cov.: 33 AF XY: 0.160 AC XY: 11930 AN XY: 74426

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0877

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0834

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.135

Alfa AF: 0.129 Hom.: 1427

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 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	-0.81
CADD	Benign	7.9
DANN	Benign	0.82

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: rs6442154; hg19: chr3-10168785;