rs17523519

Variant names:

• chr17-44345007-TC-T
• rs17523519
• ENST00000588170.5:n.-238delC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000588170.5(GRN):​n.-238delC variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,772 control chromosomes in the GnomAD database, including 13,725 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (13724 hom., cov: 0)
  • Exomes 𝑓: 0.24 (1 hom.)
• Consequence: GRN ENST00000588170.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

Genes affected

GRN (HGNC:4601): (granulin precursor) Granulins are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and PC cell-derived growth factor. Cleavage of the signal peptide produces mature granulin which can be further cleaved into a variety of active, 6 kDa peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Epithelins 1 and 2 are synonymous with granulins A and B, respectively. Both the peptides and intact granulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRN	ENST00000588170.5	n.-238delC		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60243 AN: 151584 Hom.: 13684 Cov.: 0

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.243 AC: 17 AN: 70 Hom.: 1 AF XY: 0.227 AC XY: 10 AN XY: 44

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.233

GnomAD4 genome AF: 0.398 AC: 60339 AN: 151702 Hom.: 13724 Cov.: 0 AF XY: 0.409 AC XY: 30313 AN XY: 74126

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.374

Alfa AF: 0.332 Hom.: 1120

Bravo AF: 0.409

Asia WGS AF: 0.690 AC: 2398 AN: 3478

ClinVar

Not reported in ClinVar

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: rs17523519; hg19: chr17-42422375;