rs67626468

Variant names:

• chr3-10119834-C-A
• rs67626468
• NM_018462.5:c.118+4015C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018462.5(BRK1):​c.118+4015C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,000 control chromosomes in the GnomAD database, including 2,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2609 hom., cov: 32)
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.441
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 3-10119834-C-A is Benign according to our data. Variant chr3-10119834-C-A is described in ClinVar as Benign. ClinVar VariationId is 1174440.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 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+4015C>A		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+4015C>A		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.178+864C>A		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24957 AN: 151882 Hom.: 2597 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.164 AC: 25001 AN: 152000 Hom.: 2609 Cov.: 32 AF XY: 0.162 AC XY: 12007 AN XY: 74282

African (AFR) AF: 0.292 AC: 12097 AN: 41448

American (AMR) AF: 0.129 AC: 1970 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0876 AC: 304 AN: 3472

East Asian (EAS) AF: 0.0343 AC: 178 AN: 5182

South Asian (SAS) AF: 0.170 AC: 819 AN: 4804

European-Finnish (FIN) AF: 0.0838 AC: 885 AN: 10560

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8276 AN: 67970

Other (OTH) AF: 0.145 AC: 307 AN: 2110

Alfa AF: 0.153 Hom.: 286

Bravo AF: 0.173

Asia WGS AF: 0.135 AC: 471 AN: 3478

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
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.33
DANN	Benign	0.70
PhyloP100		-0.44
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: rs67626468; hg19: chr3-10161518;