chr3-10118114-A-G

Position:

• chr3-10118114-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+2295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,912 control chromosomes in the GnomAD database, including 3,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3651 hom., cov: 30)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.792

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=-1.03).
• BP6: Variant 3-10118114-A-G is Benign according to our data. Variant chr3-10118114-A-G is described in ClinVar as [Benign]. Clinvar id is 1227069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRK1	NM_018462.5	c.118+2295A>G		intron_variant		ENST00000530758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRK1	ENST00000530758.2	c.118+2295A>G		intron_variant		1	NM_018462.5	P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30916 AN: 151794 Hom.: 3644 Cov.: 30

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0930

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.204 AC: 30956 AN: 151912 Hom.: 3651 Cov.: 30 AF XY: 0.199 AC XY: 14810 AN XY: 74268

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0929

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.178

Alfa AF: 0.185 Hom.: 374

Bravo AF: 0.214

Asia WGS AF: 0.147 AC: 512 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	-1.0
CADD	Benign	1.5
DANN	Benign	0.45

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: rs60172687; hg19: chr3-10159798;