rs2294436

Positions:

• chr6-8057455-A-G

Variant summary

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

The NM_201280.3(BLOC1S5):​c.195+5079T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,206 control chromosomes in the GnomAD database, including 1,936 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 0.16 (1936 hom., cov: 32)
• Consequence: BLOC1S5 NM_201280.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLOC1S5	NM_201280.3	c.195+5079T>C		intron_variant		ENST00000397457.7
BLOC1S5-TXNDC5	NR_037616.1	n.233+5079T>C		intron_variant, non_coding_transcript_variant
EEF1E1-BLOC1S5	NR_037618.1	n.541+5079T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLOC1S5	ENST00000397457.7	c.195+5079T>C		intron_variant		1	NM_201280.3	P1
BLOC1S5	ENST00000244777.6	c.195+5079T>C		intron_variant, NMD_transcript_variant		1
BLOC1S5	ENST00000627748.2	c.196-3083T>C		intron_variant, NMD_transcript_variant		1
BLOC1S5	ENST00000543936.7	c.195+5079T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23769 AN: 152088 Hom.: 1933 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0725

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.156 AC: 23785 AN: 152206 Hom.: 1936 Cov.: 32 AF XY: 0.155 AC XY: 11557 AN XY: 74418

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.0864

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.147

Alfa AF: 0.157 Hom.: 1092

Bravo AF: 0.157

Asia WGS AF: 0.113 AC: 391 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	6.7
DANN	Benign	0.70

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: rs2294436; hg19: chr6-8057688;