Variant rs9897526 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.264+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,786 control chromosomes in the GnomAD database, including 19,862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4235 hom., cov: 33)

Exomes 𝑓: 0.13 ( 15627 hom. )

Consequence

GRN
NM_002087.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.99

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:

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=-0.89).

BP6

Variant 17-44349572-G-A is Benign according to our data. Variant chr17-44349572-G-A is described in ClinVar as [Benign]. Clinvar id is 558916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-44349572-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRN	NM_002087.4 linkuse as main transcript	c.264+21G>A		intron_variant		ENST00000053867.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRN	ENST00000053867.8 linkuse as main transcript	c.264+21G>A		intron_variant		1	NM_002087.4	P1	P28799-1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30343

AN:

152128

Hom.:

4203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.0898

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.159

AC:

39920

AN:

250706

Hom.:

4216

AF XY:

0.163

AC XY:

22171

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.398

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.0924

Gnomad SAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.131

AC:

190911

AN:

1461540

Hom.:

15627

Cov.:

AF XY:

0.135

AC XY:

98345

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.405

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.0904

Gnomad4 SAS exome

AF:

0.307

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.200

AC:

30424

AN:

152246

Hom.:

4235

Cov.:

AF XY:

0.201

AC XY:

14958

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.392

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.0901

Gnomad4 SAS

AF:

0.324

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.132

Hom.:

1484

Bravo

AF:

0.203

Asia WGS

AF:

0.241

AC:

838

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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	Dec 15, 2015	- -

Neuronal ceroid lipofuscinosis 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

GRN-related frontotemporal lobar degeneration with Tdp43 inclusions

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.019

DANN

Benign

0.46

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