Variant chr6-8054272-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_201280.3(BLOC1S5):c.195+8262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 452,292 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0075 ( 11 hom., cov: 33)

Exomes 𝑓: 0.00087 ( 3 hom. )

Consequence

BLOC1S5
NM_201280.3 intron

Scores

Splicing: ADA: 0.00001157

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.263

Variant links:

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 links:

BLOC1S5-TXNDC5 (HGNC:):

BLOC1S5-TXNDC5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-8054272-T-C is Benign according to our data. Variant chr6-8054272-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3056960.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00755 (1149/152270) while in subpopulation AFR AF= 0.0262 (1087/41530). AF 95% confidence interval is 0.0249. There are 11 homozygotes in gnomad4. There are 546 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
BLOC1S5	NM_201280.3 linkuse as main transcript	c.195+8262A>G	intron_variant	ENST00000397457.7
BLOC1S5-TXNDC5	NR_037616.1 linkuse as main transcript	n.233+8262A>G	intron_variant, non_coding_transcript_variant
EEF1E1-BLOC1S5	NR_037618.1 linkuse as main transcript	n.541+8262A>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLOC1S5	ENST00000397457.7 linkuse as main transcript	c.195+8262A>G	intron_variant		1	NM_201280.3	P1	Q8TDH9-1
BLOC1S5	ENST00000244777.6 linkuse as main transcript	c.195+8262A>G	intron_variant, NMD_transcript_variant		1
BLOC1S5	ENST00000627748.2 linkuse as main transcript	c.*89A>G	splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	3/6	1
BLOC1S5	ENST00000543936.7 linkuse as main transcript	c.195+8262A>G	intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00747

AC:

1137

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00140

AC:

183

AN:

130398

Hom.:

AF XY:

0.00115

AC XY:

AN XY:

71346

show subpopulations

Gnomad AFR exome

AF:

0.0239

Gnomad AMR exome

AF:

0.000961

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000462

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000963

Gnomad OTH exome

AF:

0.00125

GnomAD4 exome

AF:

0.000873

AC:

262

AN:

300022

Hom.:

Cov.:

AF XY:

0.000689

AC XY:

118

AN XY:

171280

show subpopulations

Gnomad4 AFR exome

AF:

0.0234

Gnomad4 AMR exome

AF:

0.000928

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000851

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000317

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.00755

AC:

1149

AN:

152270

Hom.:

Cov.:

AF XY:

0.00733

AC XY:

546

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0262

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00322

Hom.:

Bravo

AF:

0.00846

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BLOC1S5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 26, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.8

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over