3-10118252-C-A

Variant names:

• chr3-10118252-C-A
• rs1177674519
• NM_018462.5:c.118+2433C>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+2433C>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 0.053 (0 hom., cov: 10)
  • Failed GnomAD Quality Control
• Consequence: BRK1 NM_018462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.619
• 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=-0.9).
• BP6: Variant 3-10118252-C-A is Benign according to our data. Variant chr3-10118252-C-A is described in ClinVar as Benign. ClinVar VariationId is 1238958.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+2433C>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+2433C>A		intron	N/A	ENSP00000432472.1	Q8WUW1-1
	BRK1	ENST00000916415.1		c.114-654C>A		intron	N/A	ENSP00000586474.1

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 3459 AN: 64854 Hom.: 0 Cov.: 10

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.0842

Gnomad AMR AF: 0.0542

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.0590

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0726

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: 0.0533 AC: 3459 AN: 64866 Hom.: 0 Cov.: 10 AF XY: 0.0526 AC XY: 1607 AN XY: 30536

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

African (AFR) AF: 0.0347 AC: 651 AN: 18744

American (AMR) AF: 0.0542 AC: 302 AN: 5570

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 110 AN: 1522

East Asian (EAS) AF: 0.0740 AC: 140 AN: 1892

South Asian (SAS) AF: 0.0598 AC: 112 AN: 1872

European-Finnish (FIN) AF: 0.0474 AC: 146 AN: 3080

Middle Eastern (MID) AF: 0.0682 AC: 6 AN: 88

European-Non Finnish (NFE) AF: 0.0615 AC: 1896 AN: 30832

Other (OTH) AF: 0.0719 AC: 62 AN: 862

⚠️ 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: 0.0994 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	-0.90
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		-0.62

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1177674519; hg19: chr3-10159936;