3-10119207-A-G

Position:

• chr3-10119207-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018462.5(BRK1):​c.118+3388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,528 control chromosomes in the GnomAD database, including 5,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (5494 hom., cov: 30)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-10119207-A-G is Benign according to our data. Variant chr3-10119207-A-G is described in ClinVar as [Benign]. Clinvar id is 1291099.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRK1	NM_018462.5	c.118+3388A>G		intron_variant		ENST00000530758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRK1	ENST00000530758.2	c.118+3388A>G		intron_variant		1	NM_018462.5	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34999 AN: 151420 Hom.: 5493 Cov.: 30

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.231 AC: 34999 AN: 151528 Hom.: 5494 Cov.: 30 AF XY: 0.231 AC XY: 17093 AN XY: 73966

Gnomad4 AFR AF: 0.0594

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0673

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.243

Alfa AF: 0.288 Hom.: 928

Bravo AF: 0.207

Asia WGS AF: 0.0420 AC: 148 AN: 3478

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

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.86

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: rs811907; hg19: chr3-10160891;