dbSNP rs186991064: HPS5:c.825-16T>C (chr11-18305509-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_181507.2(HPS5):c.825-16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,556,020 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

HPS5
NM_181507.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.50

Publications

0 publications found

Variant links:

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, ClinGen, Labcorp Genetics (formerly Invitae)
Hermansky-Pudlak syndrome without pulmonary fibrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

HPS5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-18305509-A-G is Benign according to our data. Variant chr11-18305509-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00106 (162/152288) while in subpopulation AMR AF = 0.00118 (18/15298). AF 95% confidence interval is 0.000928. There are 1 homozygotes in GnomAd4. There are 79 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HPS5	NM_181507.2	MANE Select	c.825-16T>C	intron	N/A	NP_852608.1	Q9UPZ3-1
HPS5	NM_001440902.1		c.825-16T>C	intron	N/A	NP_001427831.1
HPS5	NM_001440903.1		c.825-16T>C	intron	N/A	NP_001427832.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HPS5	ENST00000349215.8	TSL:1 MANE Select	c.825-16T>C	intron	N/A	ENSP00000265967.5	Q9UPZ3-1
HPS5	ENST00000396253.7	TSL:1	c.483-16T>C	intron	N/A	ENSP00000379552.3	Q9UPZ3-2
HPS5	ENST00000438420.6	TSL:1	c.483-16T>C	intron	N/A	ENSP00000399590.2	Q9UPZ3-2

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00133

AC:

334

AN:

250618

AF XY:

0.00129

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.0131

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00146

AC:

2051

AN:

1403732

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1003

AN XY:

701952

show subpopulations

African (AFR)

AF:

0.000280

AC:

AN:

32190

American (AMR)

AF:

0.00141

AC:

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

348

AN:

25788

East Asian (EAS)

AF:

0.00

AC:

AN:

39334

South Asian (SAS)

AF:

0.000495

AC:

AN:

84874

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53158

Middle Eastern (MID)

AF:

0.00159

AC:

AN:

5658

European-Non Finnish (NFE)

AF:

0.00135

AC:

1435

AN:

1059800

Other (OTH)

AF:

0.00247

AC:

144

AN:

58348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

166

248

331

414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00106

AC:

162

AN:

152288

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41552

American (AMR)

AF:

0.00118

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00113

AC:

AN:

68030

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00290

Hom.:

Bravo

AF:

0.00106

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.1

(source)

DANN

Benign

0.74

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over