rs4763829

Positions:

• chr12-12437540-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BORCS5	NM_058169.6	c.360+1755A>G		intron_variant		ENST00000314565.9	NP_477517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BORCS5	ENST00000314565.9	c.360+1755A>G		intron_variant		1	NM_058169.6	ENSP00000321546	P1
BORCS5	ENST00000298571.6	c.216+1755A>G		intron_variant		1		ENSP00000298571
BORCS5	ENST00000542728.5	c.303+1755A>G		intron_variant		3		ENSP00000443023

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

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.562

Alfa AF: 0.608 Hom.: 4862

Bravo AF: 0.621

Asia WGS AF: 0.310 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.94
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs4763829; hg19: chr12-12590474;