NM_018462.5:c.118+3324C>A

Variant names:

• chr3-10119143-C-A
• rs902058438
• NM_018462.5:c.118+3324C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_018462.5(BRK1):​c.118+3324C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (0 hom., cov: 11)
  • Failed GnomAD Quality Control
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.212
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-10119143-C-A is Benign according to our data. Variant chr3-10119143-C-A is described in ClinVar as Benign. ClinVar VariationId is 1248233.Status of the report is criteria_provided_single_submitter, 1 stars.

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+3324C>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+3324C>A		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.178+173C>A		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 3078 AN: 65306 Hom.: 0 Cov.: 11

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.0656

Gnomad AMR AF: 0.0670

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.0529

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0495

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0472 AC: 3084 AN: 65332 Hom.: 0 Cov.: 11 AF XY: 0.0516 AC XY: 1583 AN XY: 30652

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0266 AC: 540 AN: 20330

American (AMR) AF: 0.0675 AC: 378 AN: 5602

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 94 AN: 1530

East Asian (EAS) AF: 0.0529 AC: 90 AN: 1702

South Asian (SAS) AF: 0.0359 AC: 65 AN: 1812

European-Finnish (FIN) AF: 0.119 AC: 324 AN: 2714

Middle Eastern (MID) AF: 0.119 AC: 10 AN: 84

European-Non Finnish (NFE) AF: 0.0500 AC: 1519 AN: 30374

Other (OTH) AF: 0.0489 AC: 40 AN: 818

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0137 Hom.: 0

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	-0.94
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		0.21
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: rs902058438; hg19: chr3-10160827;