NM_022081.6:c.*1237_*1246delCGCGCGCGCG

Variant names:

• chr22-26451986-ACGCGCGCGCG-A
• rs10573454
• NM_022081.6:c.*1237_*1246delCGCGCGCGCG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_022081.6(HPS4):​c.*1237_*1246delCGCGCGCGCG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 14,034 control chromosomes in the GnomAD database, including 526 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (4906 hom., cov: 0)
  • Exomes 𝑓: 0.27 (526 hom.)
  • Failed GnomAD Quality Control
• Consequence: HPS4 NM_022081.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.278

Genes affected

HPS4 (HGNC:15844): (HPS4 biogenesis of lysosomal organelles complex 3 subunit 2) This gene encodes a protein component of biogenesis of lysosome-related organelles complexes (BLOC). BLOC complexes are important for the formation of endosomal-lysosomal organelles such as melanosomes and platelet dense granules. Mutations in this gene result in subtype 4 of Hermansky-Pudlak syndrome, a form of albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-26451986-ACGCGCGCGCG-A is Benign according to our data. Variant chr22-26451986-ACGCGCGCGCG-A is described in ClinVar as [Benign]. Clinvar id is 340976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS4	NM_022081.6	c.*1237_*1246delCGCGCGCGCG		3_prime_UTR_variant	Exon 14 of 14	ENST00000398145.7	NP_071364.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS4	ENST00000398145	c.*1237_*1246delCGCGCGCGCG		3_prime_UTR_variant	Exon 14 of 14	1	NM_022081.6	ENSP00000381213.2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 34753 AN: 134394 Hom.: 4907 Cov.: 0

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.272 AC: 3822 AN: 14034 Hom.: 526 AF XY: 0.276 AC XY: 2188 AN XY: 7930

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.258 AC: 34760 AN: 134474 Hom.: 4906 Cov.: 0 AF XY: 0.257 AC XY: 16706 AN XY: 64928

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.261

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hermansky-Pudlak syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10573454; hg19: chr22-26847952;