chr17-44350176-G-GAGTC

Position:

• chr17-44350176-G-GAGTC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002087.4(GRN):​c.350-50_350-47dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8862 hom., cov: 0)
  • Exomes 𝑓: 0.25 (37274 hom.)
• Consequence: GRN NM_002087.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.175

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 -16 ACMG points.

• BP6: Variant 17-44350176-G-GAGTC is Benign according to our data. Variant chr17-44350176-G-GAGTC is described in ClinVar as [Benign]. Clinvar id is 803426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRN	NM_002087.4	c.350-50_350-47dup		intron_variant		ENST00000053867.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRN	ENST00000053867.8	c.350-50_350-47dup		intron_variant		1	NM_002087.4	P1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48705 AN: 151572 Hom.: 8850 Cov.: 0

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.309

GnomAD4 exome AF: 0.248 AC: 267622 AN: 1078078 Hom.: 37274 Cov.: 16 AF XY: 0.251 AC XY: 139058 AN XY: 553102

Gnomad4 AFR exome AF: 0.467

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.507

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.321 AC: 48741 AN: 151690 Hom.: 8862 Cov.: 0 AF XY: 0.323 AC XY: 23924 AN XY: 74142

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.308

Alfa AF: 0.286 Hom.: 732

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 17, 2018

- -

GRN-related frontotemporal lobar degeneration with Tdp43 inclusions Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

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: rs34424835; hg19: chr17-42427544;