rs2743992

Positions:

• chr6-8054489-T-C

Variant summary

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

The NM_201280.3(BLOC1S5):​c.195+8045A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 277,144 control chromosomes in the GnomAD database, including 8,625 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 0.21 (4388 hom., cov: 33)
  • Exomes 𝑓: 0.24 (4237 hom.)
• Consequence: BLOC1S5 NM_201280.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.689

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]

BLOC1S5-TXNDC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLOC1S5	NM_201280.3	c.195+8045A>G		intron_variant		ENST00000397457.7
BLOC1S5-TXNDC5	NR_037616.1	n.233+8045A>G		intron_variant, non_coding_transcript_variant
EEF1E1-BLOC1S5	NR_037618.1	n.541+8045A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLOC1S5	ENST00000397457.7	c.195+8045A>G		intron_variant		1	NM_201280.3	P1
BLOC1S5	ENST00000244777.6	c.195+8045A>G		intron_variant, NMD_transcript_variant		1
BLOC1S5	ENST00000627748.2	c.196-117A>G		intron_variant, NMD_transcript_variant		1
BLOC1S5	ENST00000543936.7	c.195+8045A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31218 AN: 152098 Hom.: 4389 Cov.: 33

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.245 AC: 30585 AN: 124928 Hom.: 4237 AF XY: 0.237 AC XY: 16455 AN XY: 69498

Gnomad4 AFR exome AF: 0.0435

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.205 AC: 31212 AN: 152216 Hom.: 4388 Cov.: 33 AF XY: 0.210 AC XY: 15660 AN XY: 74422

Gnomad4 AFR AF: 0.0490

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.176

Alfa AF: 0.235 Hom.: 2531

Bravo AF: 0.190

Asia WGS AF: 0.317 AC: 1102 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	7.6
DANN	Benign	0.81

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: rs2743992; hg19: chr6-8054722; COSMIC: COSV55242511;