3-10117393-CTTTTTTTTTTT-CTTTTTTTTTTTTT

Variant names:

• chr3-10117393-C-CTT
• rs756307171
• NM_018462.5:c.118+1593_118+1594dupTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018462.5(BRK1):​c.118+1593_118+1594dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00722 in 118,598 control chromosomes in the GnomAD database, including 17 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0072 (17 hom., cov: 21)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00722 (856/118598) while in subpopulation SAS AF = 0.0235 (84/3578). AF 95% confidence interval is 0.0194. There are 17 homozygotes in GnomAd4. There are 413 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

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+1593_118+1594dupTT		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+1575insTT		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-1513_114-1512insTT		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.00722 AC: 856 AN: 118620 Hom.: 17 Cov.: 21

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.00384

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.000664

Gnomad EAS AF: 0.00139

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.000354

Gnomad MID AF: 0.00403

Gnomad NFE AF: 0.00201

Gnomad OTH AF: 0.00567

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

GnomAD4 genome AF: 0.00722 AC: 856 AN: 118598 Hom.: 17 Cov.: 21 AF XY: 0.00732 AC XY: 413 AN XY: 56384

African (AFR) AF: 0.0200 AC: 617 AN: 30816

American (AMR) AF: 0.00157 AC: 18 AN: 11448

Ashkenazi Jewish (ASJ) AF: 0.000664 AC: 2 AN: 3010

East Asian (EAS) AF: 0.00140 AC: 6 AN: 4286

South Asian (SAS) AF: 0.0235 AC: 84 AN: 3578

European-Finnish (FIN) AF: 0.000354 AC: 2 AN: 5644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 222

European-Non Finnish (NFE) AF: 0.00201 AC: 115 AN: 57218

Other (OTH) AF: 0.00565 AC: 9 AN: 1594

Alfa AF: 0.00 Hom.: 70

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

Splicing

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

Other links and lift over

dbSNP: rs756307171; hg19: chr3-10159077;