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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181507.2. 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
	HPS5	NM_181507.2	MANE Select	c.1165-15C>A		intron	N/A	NP_852608.1
	HPS5	NM_001440902.1		c.1165-15C>A		intron	N/A	NP_001427831.1
	HPS5	NM_001440903.1		c.1165-15C>A		intron	N/A	NP_001427832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS5	ENST00000349215.8	TSL:1 MANE Select	c.1165-15C>A		intron	N/A	ENSP00000265967.5
	HPS5	ENST00000396253.7	TSL:1	c.823-15C>A		intron	N/A	ENSP00000379552.3
	HPS5	ENST00000438420.6	TSL:1	c.823-15C>A		intron	N/A	ENSP00000399590.2

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Hermansky-Pudlak syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

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;