rs8531

Variant names:

• chr17-8189376-T-G
• rs8531
• NM_017622.3:c.765A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017622.3(BORCS6):​c.765A>C​(p.Pro255Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 1,601,868 control chromosomes in the GnomAD database, including 507,586 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 0.73 (42214 hom., cov: 33)
  • Exomes 𝑓: 0.79 (465372 hom.)
• Consequence: BORCS6 NM_017622.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 19 publications found

Genes affected

BORCS6 (HGNC:25939): (BLOC-1 related complex subunit 6) Enables identical protein binding activity. Involved in lysosome localization. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000279152 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.049 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS6	NM_017622.3	c.765A>C	p.Pro255Pro	synonymous_variant	Exon 1 of 1	ENST00000389017.6	NP_060092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS6	ENST00000389017.6	c.765A>C	p.Pro255Pro	synonymous_variant	Exon 1 of 1	6	NM_017622.3	ENSP00000373669.4
ENSG00000279152	ENST00000622992.1	n.444T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000299228	ENST00000761712.1	n.-108T>G		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111438 AN: 152004 Hom.: 42186 Cov.: 33

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.711

GnomAD2 exomes AF: 0.707 AC: 161089 AN: 227730 AF XY: 0.727

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.629

Gnomad EAS exome AF: 0.300

Gnomad FIN exome AF: 0.853

Gnomad NFE exome AF: 0.830

Gnomad OTH exome AF: 0.729

GnomAD4 exome AF: 0.792 AC: 1148315 AN: 1449748 Hom.: 465372 Cov.: 85 AF XY: 0.794 AC XY: 571981 AN XY: 720474

African (AFR) AF: 0.655 AC: 21686 AN: 33104

American (AMR) AF: 0.417 AC: 17745 AN: 42524

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 16209 AN: 25836

East Asian (EAS) AF: 0.288 AC: 11233 AN: 39000

South Asian (SAS) AF: 0.795 AC: 67705 AN: 85142

European-Finnish (FIN) AF: 0.858 AC: 44688 AN: 52056

Middle Eastern (MID) AF: 0.686 AC: 3936 AN: 5736

European-Non Finnish (NFE) AF: 0.832 AC: 920161 AN: 1106478

Other (OTH) AF: 0.751 AC: 44952 AN: 59872

GnomAD4 genome AF: 0.733 AC: 111508 AN: 152120 Hom.: 42214 Cov.: 33 AF XY: 0.730 AC XY: 54263 AN XY: 74370

African (AFR) AF: 0.669 AC: 27740 AN: 41476

American (AMR) AF: 0.553 AC: 8457 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2132 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1541 AN: 5150

South Asian (SAS) AF: 0.786 AC: 3791 AN: 4826

European-Finnish (FIN) AF: 0.856 AC: 9075 AN: 10600

Middle Eastern (MID) AF: 0.641 AC: 186 AN: 290

European-Non Finnish (NFE) AF: 0.829 AC: 56382 AN: 67992

Other (OTH) AF: 0.704 AC: 1484 AN: 2108

Alfa AF: 0.786 Hom.: 92353

Bravo AF: 0.702

Asia WGS AF: 0.573 AC: 1996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.73
PhyloP100		-0.049
Mutation Taster		=97/3	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: rs8531; hg19: chr17-8092694; COSMIC: COSV66504868; COSMIC: COSV66504868;