rs2743992

Positions:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.689
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]

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ACMG classification

Classification made for transcript

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
BLOC1S5NM_201280.3 linkuse as main transcriptc.195+8045A>G intron_variant ENST00000397457.7
BLOC1S5-TXNDC5NR_037616.1 linkuse as main transcriptn.233+8045A>G intron_variant, non_coding_transcript_variant
EEF1E1-BLOC1S5NR_037618.1 linkuse as main transcriptn.541+8045A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BLOC1S5ENST00000397457.7 linkuse as main transcriptc.195+8045A>G intron_variant 1 NM_201280.3 P1Q8TDH9-1
BLOC1S5ENST00000244777.6 linkuse as main transcriptc.195+8045A>G intron_variant, NMD_transcript_variant 1
BLOC1S5ENST00000627748.2 linkuse as main transcriptc.196-117A>G intron_variant, NMD_transcript_variant 1
BLOC1S5ENST00000543936.7 linkuse as main transcriptc.195+8045A>G intron_variant 2

Frequencies

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

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

Other links and lift over

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