6-8054489-T-C

Variant names:

• chr6-8054489-T-C
• rs2743992
• NM_201280.3:c.195+8045A>G

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+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
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5	NM_201280.3	MANE Select	c.195+8045A>G		intron	N/A	NP_958437.1
	BLOC1S5	NM_001199322.1		c.-100-117A>G		intron	N/A	NP_001186251.1
	BLOC1S5	NM_001199323.1		c.195+8045A>G		intron	N/A	NP_001186252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5	ENST00000397457.7	TSL:1 MANE Select	c.195+8045A>G		intron	N/A	ENSP00000380598.2
	BLOC1S5	ENST00000244777.6	TSL:1	n.195+8045A>G		intron	N/A	ENSP00000244777.2
	EEF1E1-BLOC1S5	ENST00000397456.2	TSL:3	n.*11+8045A>G		intron	N/A	ENSP00000380597.2

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

African (AFR) AF: 0.0435 AC: 119 AN: 2736

American (AMR) AF: 0.199 AC: 819 AN: 4124

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 600 AN: 2796

East Asian (EAS) AF: 0.545 AC: 2148 AN: 3944

South Asian (SAS) AF: 0.186 AC: 4532 AN: 24312

European-Finnish (FIN) AF: 0.327 AC: 1975 AN: 6038

Middle Eastern (MID) AF: 0.111 AC: 121 AN: 1086

European-Non Finnish (NFE) AF: 0.254 AC: 18719 AN: 73764

Other (OTH) AF: 0.253 AC: 1552 AN: 6128

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

African (AFR) AF: 0.0490 AC: 2039 AN: 41576

American (AMR) AF: 0.191 AC: 2926 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3472

East Asian (EAS) AF: 0.553 AC: 2863 AN: 5176

South Asian (SAS) AF: 0.195 AC: 940 AN: 4830

European-Finnish (FIN) AF: 0.345 AC: 3647 AN: 10566

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17548 AN: 67990

Other (OTH) AF: 0.176 AC: 371 AN: 2106

Alfa AF: 0.236 Hom.: 2806

Bravo AF: 0.190

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.6
DANN	Benign	0.81
PhyloP100		-0.69
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: rs2743992; hg19: chr6-8054722; COSMIC: COSV55242511;