rs1804689

Variant names:

• chr10-98445350-G-T
• rs1804689
• NM_000195.5:c.-51C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-98445350-G-T
• chr10-98445350-G-C

Variant summary

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

The NM_000195.5(HPS1):​c.-51C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,854 control chromosomes in the GnomAD database, including 7,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7012 hom., cov: 32)
  • Exomes 𝑓: 0.32 (41 hom.)
• Consequence: HPS1 NM_000195.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.83
• Publications: 9 publications found

Genes affected

HPS1 (HGNC:5163): (HPS1 biogenesis of lysosomal organelles complex 3 subunit 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is a component of three different protein complexes termed biogenesis of lysosome-related organelles complex (BLOC)-3, BLOC4, and BLOC5. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 1. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on chromosome 22. [provided by RefSeq, Aug 2015]

HPS1 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Hermansky-Pudlak syndrome with pulmonary fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289758 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 10-98445350-G-T is Benign according to our data. Variant chr10-98445350-G-T is described in ClinVar as Benign. ClinVar VariationId is 298358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000195.5. 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
	HPS1	NM_000195.5	MANE Select	c.-51C>A		5_prime_UTR	Exon 2 of 20	NP_000186.2
	HPS1	NM_001322476.2		c.-51C>A		5_prime_UTR	Exon 2 of 20	NP_001309405.1	Q92902-1
	HPS1	NM_001322477.2		c.-51C>A		5_prime_UTR	Exon 2 of 20	NP_001309406.1	Q92902-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS1	ENST00000361490.9	TSL:1 MANE Select	c.-51C>A		5_prime_UTR	Exon 2 of 20	ENSP00000355310.4	Q92902-1
	HPS1	ENST00000338546.9	TSL:1	c.-51C>A		5_prime_UTR	Exon 2 of 10	ENSP00000343638.5	Q92902-3
	HPS1	ENST00000467246.5	TSL:1	n.-51C>A		non_coding_transcript_exon	Exon 2 of 19	ENSP00000514163.1	A0A8V8TP71

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43369 AN: 151972 Hom.: 7014 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.325 AC: 248 AN: 764 Hom.: 41 Cov.: 0 AF XY: 0.344 AC XY: 152 AN XY: 442

African (AFR) AF: 0.111 AC: 2 AN: 18

American (AMR) AF: 0.250 AC: 2 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 6 AN: 16

East Asian (EAS) AF: 0.391 AC: 61 AN: 156

South Asian (SAS) AF: 0.250 AC: 2 AN: 8

European-Finnish (FIN) AF: 0.306 AC: 22 AN: 72

Middle Eastern (MID) AF: 0.500 AC: 3 AN: 6

European-Non Finnish (NFE) AF: 0.315 AC: 140 AN: 444

Other (OTH) AF: 0.278 AC: 10 AN: 36

GnomAD4 genome AF: 0.285 AC: 43377 AN: 152090 Hom.: 7012 Cov.: 32 AF XY: 0.294 AC XY: 21857 AN XY: 74356

African (AFR) AF: 0.145 AC: 6012 AN: 41506

American (AMR) AF: 0.377 AC: 5766 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3470

East Asian (EAS) AF: 0.427 AC: 2201 AN: 5150

South Asian (SAS) AF: 0.421 AC: 2030 AN: 4820

European-Finnish (FIN) AF: 0.407 AC: 4306 AN: 10578

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21094 AN: 67968

Other (OTH) AF: 0.279 AC: 589 AN: 2108

Alfa AF: 0.285 Hom.: 2066

Bravo AF: 0.274

Asia WGS AF: 0.389 AC: 1352 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hermansky-Pudlak syndrome 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs1804689; hg19: chr10-100205107;