11-18301970-T-C

Variant names:

• chr11-18301970-T-C
• rs4353250
• NM_181507.2:c.897-1054A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181507.2(HPS5):​c.897-1054A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 151,840 control chromosomes in the GnomAD database, including 40,474 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 0.73 (40474 hom., cov: 29)
• Consequence: HPS5 NM_181507.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.724
• Publications: 23 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS5	NM_181507.2	c.897-1054A>G		intron_variant	Intron 8 of 22	ENST00000349215.8	NP_852608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS5	ENST00000349215.8	c.897-1054A>G		intron_variant	Intron 8 of 22	1	NM_181507.2	ENSP00000265967.5
HPS5	ENST00000396253.7	c.555-1054A>G		intron_variant	Intron 7 of 21	1		ENSP00000379552.3
HPS5	ENST00000438420.6	c.555-1054A>G		intron_variant	Intron 7 of 21	1		ENSP00000399590.2
HPS5	ENST00000531848.1	c.555-1054A>G		intron_variant	Intron 7 of 10	5		ENSP00000431758.1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110153 AN: 151722 Hom.: 40426 Cov.: 29

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.726 AC: 110257 AN: 151840 Hom.: 40474 Cov.: 29 AF XY: 0.730 AC XY: 54142 AN XY: 74212

African (AFR) AF: 0.764 AC: 31614 AN: 41382

American (AMR) AF: 0.746 AC: 11372 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2045 AN: 3462

East Asian (EAS) AF: 0.968 AC: 5001 AN: 5164

South Asian (SAS) AF: 0.750 AC: 3610 AN: 4814

European-Finnish (FIN) AF: 0.719 AC: 7571 AN: 10524

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46671 AN: 67928

Other (OTH) AF: 0.713 AC: 1505 AN: 2110

Alfa AF: 0.699 Hom.: 113277

Bravo AF: 0.732

Asia WGS AF: 0.889 AC: 3086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	9.1
DANN	Benign	0.74
PhyloP100		-0.72
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: rs4353250; hg19: chr11-18323517;