11-18304509-G-A

Position:

• chr11-18304509-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181507.2(HPS5):​c.896+913C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,032 control chromosomes in the GnomAD database, including 1,576 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1576 hom., cov: 32)
• Consequence: HPS5 NM_181507.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS5	NM_181507.2	c.896+913C>T		intron_variant		ENST00000349215.8	NP_852608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS5	ENST00000349215.8	c.896+913C>T		intron_variant		1	NM_181507.2	ENSP00000265967	P1
HPS5	ENST00000396253.7	c.554+913C>T		intron_variant		1		ENSP00000379552
HPS5	ENST00000438420.6	c.554+913C>T		intron_variant		1		ENSP00000399590
HPS5	ENST00000531848.1	c.554+913C>T		intron_variant		5		ENSP00000431758

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21178 AN: 151914 Hom.: 1573 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.156

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: 0.103

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.139 AC: 21192 AN: 152032 Hom.: 1576 Cov.: 32 AF XY: 0.142 AC XY: 10576 AN XY: 74292

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.151

Alfa AF: 0.0703 Hom.: 76

Bravo AF: 0.140

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs11024611; hg19: chr11-18326056;