3-10118252-C-CAAAAAA

Position:

• chr3-10118252-C-CAAAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018462.5(BRK1):​c.118+2446_118+2451dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 66,588 control chromosomes in the GnomAD database, including 150 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.092 (150 hom., cov: 27)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.685

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 -10 ACMG points.

• BP6: Variant 3-10118252-C-CAAAAAA is Benign according to our data. Variant chr3-10118252-C-CAAAAAA is described in ClinVar as [Benign]. Clinvar id is 1250650.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRK1	NM_018462.5	c.118+2446_118+2451dup		intron_variant		ENST00000530758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRK1	ENST00000530758.2	c.118+2446_118+2451dup		intron_variant		1	NM_018462.5	P1

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 6105 AN: 66576 Hom.: 150 Cov.: 27

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0757

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.0686

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0797

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

GnomAD4 genome AF: 0.0916 AC: 6102 AN: 66588 Hom.: 150 Cov.: 27 AF XY: 0.0850 AC XY: 2646 AN XY: 31140

Gnomad4 AFR AF: 0.0455

Gnomad4 AMR AF: 0.0755

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.00909

Gnomad4 SAS AF: 0.0515

Gnomad4 FIN AF: 0.0423

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.0790

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

Aug 16, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs59622736; hg19: chr3-10159936;