NM_018462.5:c.118+1594dupT

Variant names:

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

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+1594dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 118,644 control chromosomes in the GnomAD database, including 2,007 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2007 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-C-CT is Benign according to our data. Variant chr3-10117393-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1227437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 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+1594dupT		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+1574_118+1575insT		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-1513_114-1512insT		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 18877 AN: 118666 Hom.: 2009 Cov.: 21

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.0302

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0443

Gnomad MID AF: 0.0968

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.159 AC: 18873 AN: 118644 Hom.: 2007 Cov.: 21 AF XY: 0.153 AC XY: 8611 AN XY: 56406

African (AFR) AF: 0.245 AC: 7544 AN: 30812

American (AMR) AF: 0.119 AC: 1363 AN: 11452

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 275 AN: 3008

East Asian (EAS) AF: 0.0301 AC: 129 AN: 4292

South Asian (SAS) AF: 0.129 AC: 461 AN: 3580

European-Finnish (FIN) AF: 0.0443 AC: 250 AN: 5646

Middle Eastern (MID) AF: 0.0766 AC: 17 AN: 222

European-Non Finnish (NFE) AF: 0.149 AC: 8517 AN: 57252

Other (OTH) AF: 0.133 AC: 212 AN: 1598

Alfa AF: 0.0331 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 (auto)

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;