rs2815142

Positions:

• chr6-8043313-G-A
• chr6-8043313-G-C
• chr6-8043313-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201280.3(BLOC1S5):​c.196-2045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,978 control chromosomes in the GnomAD database, including 25,532 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 0.56 (25532 hom., cov: 31)
• Consequence: BLOC1S5 NM_201280.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450

Genes affected

BLOC1S5 (HGNC:18561): (biogenesis of lysosomal organelles complex 1 subunit 5) This gene encodes a component of BLOC-1 (biogenesis of lysosome-related organelles complex 1). Components of this complex are involved in the biogenesis of organelles such as melanosomes and platelet-dense granules. A mouse model for Hermansky-Pudlak Syndrome is mutated in the murine version of this gene. Alternative splicing results in multiple transcript variants. Read-through transcription exists between this gene and the upstream EEF1E1 (eukaryotic translation elongation factor 1 epsilon 1) gene, as well as with the downstream TXNDC5 (thioredoxin domain containing 5) gene. [provided by RefSeq, Dec 2010]

EEF1E1-BLOC1S5 (HGNC:49187): (EEF1E1-BLOC1S5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring EEF1E1 (eukaryotic translation elongation factor 1 epsilon 1) and MUTED (muted homolog) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

BLOC1S5-TXNDC5 (HGNC:42001): (BLOC1S5-TXNDC5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MUTED (muted homolog) and TXNDC5 (thioredoxin domain containing 5) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

BLOC1S5-TXNDC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLOC1S5	NM_201280.3	c.196-2045C>T		intron_variant		ENST00000397457.7	NP_958437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLOC1S5	ENST00000397457.7	c.196-2045C>T		intron_variant		1	NM_201280.3	ENSP00000380598.2
EEF1E1-BLOC1S5	ENST00000397456.2	n.*12-2045C>T		intron_variant		3		ENSP00000380597.2
BLOC1S5-TXNDC5	ENST00000439343.2	n.184-2045C>T		intron_variant		2		ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85410 AN: 151860 Hom.: 25529 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.562 AC: 85438 AN: 151978 Hom.: 25532 Cov.: 31 AF XY: 0.567 AC XY: 42152 AN XY: 74290

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.528

Alfa AF: 0.600 Hom.: 11410

Bravo AF: 0.550

Asia WGS AF: 0.757 AC: 2627 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.83

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: rs2815142; hg19: chr6-8043546;