3-10116618-C-G

Position:

• chr3-10116618-C-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+799C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,004 control chromosomes in the GnomAD database, including 5,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (5329 hom., cov: 32)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.551

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 3-10116618-C-G is Benign according to our data. Variant chr3-10116618-C-G is described in ClinVar as [Benign]. Clinvar id is 1277703.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRK1	NM_018462.5	c.118+799C>G		intron_variant		ENST00000530758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRK1	ENST00000530758.2	c.118+799C>G		intron_variant		1	NM_018462.5	P1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35432 AN: 151886 Hom.: 5322 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0934

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.233 AC: 35475 AN: 152004 Hom.: 5329 Cov.: 32 AF XY: 0.228 AC XY: 16945 AN XY: 74274

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0932

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.200

Alfa AF: 0.202 Hom.: 465

Bravo AF: 0.248

Asia WGS AF: 0.154 AC: 538 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	7.0
DANN	Benign	0.79

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: rs17032414; hg19: chr3-10158302;