rs73430857

Variant names:

• chr11-18292989-G-A
• rs73430857
• NM_181507.2:c.1785-13C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-18292989-G-A
• chr11-18292989-G-T

Variant summary

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

The NM_001440902.1(HPS5):​c.1785-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,606,272 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (101 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (75 hom.)
• Consequence: HPS5 NM_001440902.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.920
• Publications: 1 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=-0.87).
• BP6: Variant 11-18292989-G-A is Benign according to our data. Variant chr11-18292989-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440902.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS5	NM_181507.2	MANE Select	c.1785-13C>T		intron	N/A	NP_852608.1
	HPS5	NM_001440902.1		c.1785-13C>T		intron	N/A	NP_001427831.1
	HPS5	NM_001440903.1		c.1785-13C>T		intron	N/A	NP_001427832.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS5	ENST00000349215.8	TSL:1 MANE Select	c.1785-13C>T		intron	N/A	ENSP00000265967.5
	HPS5	ENST00000396253.7	TSL:1	c.1443-13C>T		intron	N/A	ENSP00000379552.3
	HPS5	ENST00000438420.6	TSL:1	c.1443-13C>T		intron	N/A	ENSP00000399590.2

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2941 AN: 151670 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00691

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00504 AC: 1266 AN: 251390 AF XY: 0.00339

Gnomad AFR exome AF: 0.0690

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00185 AC: 2684 AN: 1454484 Hom.: 75 Cov.: 29 AF XY: 0.00156 AC XY: 1132 AN XY: 724250

African (AFR) AF: 0.0663 AC: 2202 AN: 33226

American (AMR) AF: 0.00376 AC: 168 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39644

South Asian (SAS) AF: 0.000105 AC: 9 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5754

European-Non Finnish (NFE) AF: 0.0000371 AC: 41 AN: 1105446

Other (OTH) AF: 0.00416 AC: 250 AN: 60136

GnomAD4 genome AF: 0.0194 AC: 2949 AN: 151788 Hom.: 101 Cov.: 32 AF XY: 0.0187 AC XY: 1388 AN XY: 74174

African (AFR) AF: 0.0679 AC: 2809 AN: 41356

American (AMR) AF: 0.00690 AC: 105 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67968

Other (OTH) AF: 0.0119 AC: 25 AN: 2100

Alfa AF: 0.00911 Hom.: 18

Bravo AF: 0.0226

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely 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	-0.87
CADD	Benign	5.3
DANN	Benign	0.19
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73430857; hg19: chr11-18314536;