rs888200

Variant names:

• chr12-12402365-G-A
• rs888200
• NM_058169.6:c.203-33263G>A

Variant summary

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

The NM_058169.6(BORCS5):​c.203-33263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,934 control chromosomes in the GnomAD database, including 25,918 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 0.58 (25918 hom., cov: 31)
• Consequence: BORCS5 NM_058169.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS5	NM_058169.6	c.203-33263G>A		intron_variant	Intron 2 of 3	ENST00000314565.9	NP_477517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS5	ENST00000314565.9	c.203-33263G>A		intron_variant	Intron 2 of 3	1	NM_058169.6	ENSP00000321546.4
BORCS5	ENST00000298571.6	c.59-33263G>A		intron_variant	Intron 1 of 2	1		ENSP00000298571.6
BORCS5	ENST00000542728.5	c.146-33263G>A		intron_variant	Intron 2 of 3	3		ENSP00000443023.1
BORCS5	ENST00000543990.1	n.297-33263G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87325 AN: 151816 Hom.: 25878 Cov.: 31

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.575 AC: 87417 AN: 151934 Hom.: 25918 Cov.: 31 AF XY: 0.567 AC XY: 42063 AN XY: 74250

African (AFR) AF: 0.707 AC: 29279 AN: 41426

American (AMR) AF: 0.522 AC: 7973 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1819 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1463 AN: 5154

South Asian (SAS) AF: 0.341 AC: 1644 AN: 4818

European-Finnish (FIN) AF: 0.535 AC: 5627 AN: 10518

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37811 AN: 67952

Other (OTH) AF: 0.525 AC: 1108 AN: 2110

Alfa AF: 0.578 Hom.: 4632

Bravo AF: 0.583

Asia WGS AF: 0.313 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.17
DANN	Benign	0.69
PhyloP100		-1.2
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: rs888200; hg19: chr12-12555299;