rs918115

Positions:

• chr12-12463469-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BORCS5	NM_058169.6	c.361-2077T>C		intron_variant		ENST00000314565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BORCS5	ENST00000314565.9	c.361-2077T>C		intron_variant		1	NM_058169.6	P1
BORCS5	ENST00000298571.6	c.217-2077T>C		intron_variant		1
BORCS5	ENST00000542728.5	c.304-2077T>C		intron_variant		3

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

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.0466

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.235

Alfa AF: 0.275 Hom.: 3350

Bravo AF: 0.244

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.67

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: rs918115; hg19: chr12-12616403;