rs2294436

Variant names:

• chr6-8057455-A-G
• rs2294436
• NM_201280.3:c.195+5079T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201280.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5	NM_201280.3	MANE Select	c.195+5079T>C		intron	N/A	NP_958437.1	Q8TDH9-1
	BLOC1S5	NM_001199322.1		c.-100-3083T>C		intron	N/A	NP_001186251.1	Q8TDH9-3
	BLOC1S5	NM_001199323.1		c.195+5079T>C		intron	N/A	NP_001186252.1	A0A0A0MTN6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5	ENST00000397457.7	TSL:1 MANE Select	c.195+5079T>C		intron	N/A	ENSP00000380598.2	Q8TDH9-1
	BLOC1S5	ENST00000244777.6	TSL:1	n.195+5079T>C		intron	N/A	ENSP00000244777.2	G5E931
	EEF1E1-BLOC1S5	ENST00000397456.2	TSL:3	n.*11+5079T>C		intron	N/A	ENSP00000380597.2	C9J1V9

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

African (AFR) AF: 0.150 AC: 6225 AN: 41522

American (AMR) AF: 0.185 AC: 2825 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0864 AC: 300 AN: 3472

East Asian (EAS) AF: 0.128 AC: 665 AN: 5178

South Asian (SAS) AF: 0.0726 AC: 350 AN: 4822

European-Finnish (FIN) AF: 0.178 AC: 1892 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11125 AN: 67990

Other (OTH) AF: 0.147 AC: 310 AN: 2110

Alfa AF: 0.157 Hom.: 1210

Bravo AF: 0.157

Asia WGS AF: 0.113 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.7
DANN	Benign	0.70
PhyloP100		0.84
Mutation Taster		=100/0	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: rs2294436; hg19: chr6-8057688;