chr3-10118575-T-C

Position:

• chr3-10118575-T-C

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+2756T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,582 control chromosomes in the GnomAD database, including 10,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (10201 hom., cov: 30)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.27

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=-1.02).
• BP6: Variant 3-10118575-T-C is Benign according to our data. Variant chr3-10118575-T-C is described in ClinVar as [Benign]. Clinvar id is 1273697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRK1	NM_018462.5	c.118+2756T>C		intron_variant		ENST00000530758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRK1	ENST00000530758.2	c.118+2756T>C		intron_variant		1	NM_018462.5	P1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46029 AN: 151464 Hom.: 10191 Cov.: 30

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0957

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.304 AC: 46080 AN: 151582 Hom.: 10201 Cov.: 30 AF XY: 0.298 AC XY: 22057 AN XY: 74082

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.0955

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.255

Alfa AF: 0.256 Hom.: 864

Bravo AF: 0.324

Asia WGS AF: 0.165 AC: 574 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	0.58
DANN	Benign	0.35

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: rs6776176; hg19: chr3-10160259;