Variant rs850713 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002087.4(GRN):c.462+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,602,776 control chromosomes in the GnomAD database, including 52,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6050 hom., cov: 25)

Exomes 𝑓: 0.25 ( 46445 hom. )

Consequence

GRN
NM_002087.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.981

Variant links:

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]

GRN links:

GRN (HGNC:):

GRN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-44350364-G-A is Benign according to our data. Variant chr17-44350364-G-A is described in ClinVar as [Benign]. Clinvar id is 558917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-44350364-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRN	NM_002087.4 linkuse as main transcript	c.462+24G>A		intron_variant		ENST00000053867.8	NP_002078.1	P28799-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRN	ENST00000053867.8 linkuse as main transcript	c.462+24G>A		intron_variant		1	NM_002087.4	ENSP00000053867.2		P28799-1

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41338

AN:

149572

Hom.:

6049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.354

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.276

GnomAD3 exomes

AF:

0.281

AC:

70539

AN:

250930

Hom.:

10657

AF XY:

0.282

AC XY:

38323

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.492

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.246

AC:

357114

AN:

1453084

Hom.:

46445

Cov.:

AF XY:

0.248

AC XY:

179720

AN XY:

723452

show subpopulations

Gnomad4 AFR exome

AF:

0.318

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.358

Gnomad4 EAS exome

AF:

0.505

Gnomad4 SAS exome

AF:

0.314

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.223

Gnomad4 OTH exome

AF:

0.269

GnomAD4 genome

AF:

0.276

AC:

41346

AN:

149692

Hom.:

6050

Cov.:

AF XY:

0.278

AC XY:

20311

AN XY:

72962

show subpopulations

Gnomad4 AFR

AF:

0.327

Gnomad4 AMR

AF:

0.233

Gnomad4 ASJ

AF:

0.354

Gnomad4 EAS

AF:

0.490

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.299

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.276

Alfa

AF:

0.254

Hom.:

963

Bravo

AF:

0.274

Asia WGS

AF:

0.388

AC:

1354

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.9

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over