rs7128146

Variant names:

• chr11-18297732-G-T
• rs7128146
• NM_181507.2:c.1165-15C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181507.2(HPS5):​c.1165-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,608,254 control chromosomes in the GnomAD database, including 10,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1572 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9160 hom.)
• Consequence: HPS5 NM_181507.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.168
• Publications: 9 publications found

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]

HPS5 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Hermansky-Pudlak syndrome without pulmonary fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-18297732-G-T is Benign according to our data. Variant chr11-18297732-G-T is described in ClinVar as [Benign]. Clinvar id is 178779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS5	NM_181507.2	c.1165-15C>A		intron_variant	Intron 10 of 22	ENST00000349215.8	NP_852608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS5	ENST00000349215.8	c.1165-15C>A		intron_variant	Intron 10 of 22	1	NM_181507.2	ENSP00000265967.5
HPS5	ENST00000396253.7	c.823-15C>A		intron_variant	Intron 9 of 21	1		ENSP00000379552.3
HPS5	ENST00000438420.6	c.823-15C>A		intron_variant	Intron 9 of 21	1		ENSP00000399590.2
HPS5	ENST00000531848.1	c.823-15C>A		intron_variant	Intron 9 of 10	5		ENSP00000431758.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21135 AN: 152026 Hom.: 1569 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.151

GnomAD2 exomes AF: 0.136 AC: 34132 AN: 250574 AF XY: 0.131

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.119

Gnomad EAS exome AF: 0.119

Gnomad FIN exome AF: 0.161

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.105 AC: 153449 AN: 1456110 Hom.: 9160 Cov.: 30 AF XY: 0.106 AC XY: 76697 AN XY: 724814

African (AFR) AF: 0.192 AC: 6386 AN: 33294

American (AMR) AF: 0.205 AC: 9145 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3125 AN: 26092

East Asian (EAS) AF: 0.152 AC: 6038 AN: 39630

South Asian (SAS) AF: 0.126 AC: 10877 AN: 86110

European-Finnish (FIN) AF: 0.159 AC: 8378 AN: 52772

Middle Eastern (MID) AF: 0.154 AC: 882 AN: 5730

European-Non Finnish (NFE) AF: 0.0920 AC: 101859 AN: 1107570

Other (OTH) AF: 0.112 AC: 6759 AN: 60212

GnomAD4 genome AF: 0.139 AC: 21149 AN: 152144 Hom.: 1572 Cov.: 32 AF XY: 0.142 AC XY: 10561 AN XY: 74388

African (AFR) AF: 0.190 AC: 7885 AN: 41506

American (AMR) AF: 0.156 AC: 2380 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3470

East Asian (EAS) AF: 0.119 AC: 616 AN: 5180

South Asian (SAS) AF: 0.129 AC: 622 AN: 4828

European-Finnish (FIN) AF: 0.175 AC: 1848 AN: 10568

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6962 AN: 67986

Other (OTH) AF: 0.150 AC: 316 AN: 2112

Alfa AF: 0.129 Hom.: 334

Bravo AF: 0.140

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

1165-15C>A in intron 10 of HPS5: This variant is not expected to have clinical s ignificance because it has been identified in 19.6% (860/4396) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs7128146). -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hermansky-Pudlak syndrome 5 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.73
DANN	Benign	0.37
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7128146; hg19: chr11-18319279; COSMIC: COSV61687455; COSMIC: COSV61687455;