rs4763829

Variant names:

• chr12-12437540-A-G
• rs4763829
• NM_058169.6:c.360+1755A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_058169.6(BORCS5):​c.360+1755A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,024 control chromosomes in the GnomAD database, including 29,636 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (29636 hom., cov: 31)
• Consequence: BORCS5 NM_058169.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522
• Publications: 4 publications found

Genes affected

BORCS5 (HGNC:17950): (BLOC-1 related complex subunit 5) Involved in lysosome localization and organelle transport along microtubule. Located in cytoplasmic side of lysosomal membrane and plasma membrane. Is intrinsic component of membrane. Part of BORC complex. Colocalizes with plus-end kinesin complex. [provided by Alliance of Genome Resources, Apr 2022]

BORCS5 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058169.6. 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
	BORCS5	NM_058169.6	MANE Select	c.360+1755A>G		intron	N/A	NP_477517.1	Q969J3-1
	BORCS5	NM_001300742.3		c.303+1755A>G		intron	N/A	NP_001287671.1	G3V1P3
	BORCS5	NM_001330356.2		c.216+1755A>G		intron	N/A	NP_001317285.1	Q969J3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORCS5	ENST00000314565.9	TSL:1 MANE Select	c.360+1755A>G		intron	N/A	ENSP00000321546.4	Q969J3-1
	BORCS5	ENST00000298571.6	TSL:1	c.216+1755A>G		intron	N/A	ENSP00000298571.6	Q969J3-2
	BORCS5	ENST00000866053.1		c.423+1755A>G		intron	N/A	ENSP00000536112.1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92836 AN: 151906 Hom.: 29584 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.611 AC: 92947 AN: 152024 Hom.: 29636 Cov.: 31 AF XY: 0.601 AC XY: 44629 AN XY: 74290

African (AFR) AF: 0.786 AC: 32585 AN: 41454

American (AMR) AF: 0.548 AC: 8376 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1871 AN: 3466

East Asian (EAS) AF: 0.284 AC: 1466 AN: 5170

South Asian (SAS) AF: 0.321 AC: 1550 AN: 4824

European-Finnish (FIN) AF: 0.545 AC: 5752 AN: 10546

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39415 AN: 67978

Other (OTH) AF: 0.562 AC: 1183 AN: 2106

Alfa AF: 0.612 Hom.: 5084

Bravo AF: 0.621

Asia WGS AF: 0.310 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.94
DANN	Benign	0.65
PhyloP100		-0.52
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: rs4763829; hg19: chr12-12590474;