rs4757638

chr11-18291406-G-Achr11-18291406-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181507.2(HPS5):c.2440+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,365,908 control chromosomes in the GnomAD database, including 250,637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26475 hom., cov: 31)
  • Exomes 𝑓: 0.60 (224162 hom.)
• Consequence: HPS5 NM_181507.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.19

Genes affected

HPS5 (HGNC:17022): (HPS5 biogenesis of lysosomal organelles complex 2 subunit 2) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. This protein interacts with Hermansky-Pudlak syndrome 6 protein and may interact with the cytoplasmic domain of integrin, alpha-3. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 5. Multiple transcript variants encoding two distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 11-18291406-G-A is Benign according to our data. Variant chr11-18291406-G-A is described in ClinVar as [Benign]. Clinvar id is 262985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPS5	NM_181507.2	c.2440+36C>T		intron_variant		ENST00000349215.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPS5	ENST00000349215.8	c.2440+36C>T		intron_variant		1	NM_181507.2	P1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89041 AN: 151648 Hom.: 26439 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.560

GnomAD3 exomes AF: 0.591 AC: 125786 AN: 212722 Hom.: 37894 AF XY: 0.588 AC XY: 67638 AN XY: 114958

Gnomad AFR exome AF: 0.570

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.855

Gnomad SAS exome AF: 0.600

Gnomad FIN exome AF: 0.551

Gnomad NFE exome AF: 0.569

Gnomad OTH exome AF: 0.548

GnomAD4 exome AF: 0.604 AC: 733588 AN: 1214142 Hom.: 224162 Cov.: 16 AF XY: 0.602 AC XY: 368782 AN XY: 613054

Gnomad4 AFR exome AF: 0.567

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.807

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.553

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.596

GnomAD4 genome AF: 0.587 AC: 89130 AN: 151766 Hom.: 26475 Cov.: 31 AF XY: 0.588 AC XY: 43581 AN XY: 74124

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.565

Alfa AF: 0.566 Hom.: 27255

Bravo AF: 0.592

Asia WGS AF: 0.746 AC: 2589 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.053
Dann	Benign	0.75

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: rs4757638; hg19: chr11-18312953;