chr3-10117393-CT-C

Variant names:

• chr3-10117393-CT-C
• rs756307171
• NM_018462.5:c.118+1594delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018462.5(BRK1):​c.118+1594delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0503 in 118,586 control chromosomes in the GnomAD database, including 76 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.050 (76 hom., cov: 21)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.931
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-10117393-CT-C is Benign according to our data. Variant chr3-10117393-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1178812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018462.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRK1	NM_018462.5	MANE Select	c.118+1594delT		intron	N/A	NP_060932.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRK1	ENST00000530758.2	TSL:1 MANE Select	c.118+1575delT		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-1512delT		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.0503 AC: 5966 AN: 118608 Hom.: 76 Cov.: 21

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.0707

Gnomad EAS AF: 0.0564

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.0407

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.0586

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

GnomAD4 genome AF: 0.0503 AC: 5968 AN: 118586 Hom.: 76 Cov.: 21 AF XY: 0.0474 AC XY: 2674 AN XY: 56382

African (AFR) AF: 0.0384 AC: 1182 AN: 30804

American (AMR) AF: 0.0323 AC: 370 AN: 11450

Ashkenazi Jewish (ASJ) AF: 0.0707 AC: 213 AN: 3012

East Asian (EAS) AF: 0.0564 AC: 242 AN: 4290

South Asian (SAS) AF: 0.0673 AC: 241 AN: 3580

European-Finnish (FIN) AF: 0.0423 AC: 239 AN: 5646

Middle Eastern (MID) AF: 0.0455 AC: 10 AN: 220

European-Non Finnish (NFE) AF: 0.0572 AC: 3274 AN: 57208

Other (OTH) AF: 0.0583 AC: 93 AN: 1594

Alfa AF: 0.0118 Hom.: 70

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs756307171; hg19: chr3-10159077;