rs41317034

Variant names:

• chr10-98425493-C-T
• rs41317034
• NM_000195.5:c.1335+48G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-98425493-C-T
• chr10-98425493-C-G

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.1335+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 1,564,768 control chromosomes in the GnomAD database, including 6,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (790 hom., cov: 33)
  • Exomes 𝑓: 0.089 (6052 hom.)
• Consequence: HPS1 NM_000195.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.02
• Publications: 6 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=-0.87).
• BP6: Variant 10-98425493-C-T is Benign according to our data. Variant chr10-98425493-C-T is described in ClinVar as Benign. ClinVar VariationId is 255499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 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.1335+48G>A		intron	N/A	NP_000186.2
	HPS1	NM_001322476.2		c.1335+48G>A		intron	N/A	NP_001309405.1	Q92902-1
	HPS1	NM_001322477.2		c.1335+48G>A		intron	N/A	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.1335+48G>A		intron	N/A	ENSP00000355310.4	Q92902-1
	HPS1	ENST00000467246.5	TSL:1	n.*694+48G>A		intron	N/A	ENSP00000514163.1	A0A8V8TP71
	ENSG00000289758	ENST00000699159.1		n.*694+48G>A		intron	N/A	ENSP00000514167.1	A0A8V8TP71

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15063 AN: 152176 Hom.: 788 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.106 AC: 19967 AN: 188278 AF XY: 0.0998

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.190

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.0881

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.0888 AC: 125486 AN: 1412474 Hom.: 6052 Cov.: 29 AF XY: 0.0874 AC XY: 61120 AN XY: 699396

African (AFR) AF: 0.110 AC: 3604 AN: 32672

American (AMR) AF: 0.160 AC: 6187 AN: 38662

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3077 AN: 25330

East Asian (EAS) AF: 0.164 AC: 6254 AN: 38106

South Asian (SAS) AF: 0.0422 AC: 3413 AN: 80898

European-Finnish (FIN) AF: 0.113 AC: 5685 AN: 50452

Middle Eastern (MID) AF: 0.116 AC: 533 AN: 4590

European-Non Finnish (NFE) AF: 0.0840 AC: 91017 AN: 1083226

Other (OTH) AF: 0.0976 AC: 5716 AN: 58538

GnomAD4 genome AF: 0.0990 AC: 15084 AN: 152294 Hom.: 790 Cov.: 33 AF XY: 0.102 AC XY: 7588 AN XY: 74464

African (AFR) AF: 0.105 AC: 4372 AN: 41576

American (AMR) AF: 0.126 AC: 1925 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3472

East Asian (EAS) AF: 0.172 AC: 886 AN: 5164

South Asian (SAS) AF: 0.0443 AC: 214 AN: 4830

European-Finnish (FIN) AF: 0.109 AC: 1162 AN: 10618

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0842 AC: 5729 AN: 68010

Other (OTH) AF: 0.109 AC: 231 AN: 2114

Alfa AF: 0.0971 Hom.: 203

Bravo AF: 0.103

Asia WGS AF: 0.102 AC: 358 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.72
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs41317034; hg19: chr10-100185250;