chr12-12463469-T-C

Variant names:

• chr12-12463469-T-C
• rs918115
• NM_058169.6:c.361-2077T>C

Variant summary

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

The NM_058169.6(BORCS5):​c.361-2077T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,080 control chromosomes in the GnomAD database, including 5,219 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 0.25 (5219 hom., cov: 32)
• Consequence: BORCS5 NM_058169.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORCS5	NM_058169.6	MANE Select	c.361-2077T>C		intron	N/A	NP_477517.1
	BORCS5	NM_001300742.3		c.304-2077T>C		intron	N/A	NP_001287671.1
	BORCS5	NM_001330356.2		c.217-2077T>C		intron	N/A	NP_001317285.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORCS5	ENST00000314565.9	TSL:1 MANE Select	c.361-2077T>C		intron	N/A	ENSP00000321546.4
	BORCS5	ENST00000298571.6	TSL:1	c.217-2077T>C		intron	N/A	ENSP00000298571.6
	BORCS5	ENST00000542728.5	TSL:3	c.304-2077T>C		intron	N/A	ENSP00000443023.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38005 AN: 151962 Hom.: 5219 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.250 AC: 38025 AN: 152080 Hom.: 5219 Cov.: 32 AF XY: 0.252 AC XY: 18702 AN XY: 74338

African (AFR) AF: 0.171 AC: 7089 AN: 41502

American (AMR) AF: 0.306 AC: 4677 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 922 AN: 3468

East Asian (EAS) AF: 0.0466 AC: 241 AN: 5170

South Asian (SAS) AF: 0.162 AC: 779 AN: 4814

European-Finnish (FIN) AF: 0.358 AC: 3783 AN: 10554

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19770 AN: 67972

Other (OTH) AF: 0.235 AC: 496 AN: 2112

Alfa AF: 0.280 Hom.: 4478

Bravo AF: 0.244

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.67
PhyloP100		0.34
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: rs918115; hg19: chr12-12616403;