rs3785817

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002087.4(GRN):​c.-8+963A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,082 control chromosomes in the GnomAD database, including 6,625 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6612 hom., cov: 31)
Exomes 𝑓: 0.31 ( 13 hom. )

Consequence

GRN
NM_002087.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.792
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRNNM_002087.4 linkuse as main transcriptc.-8+963A>G intron_variant ENST00000053867.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRNENST00000053867.8 linkuse as main transcriptc.-8+963A>G intron_variant 1 NM_002087.4 P1P28799-1

Frequencies

GnomAD3 genomes
AF:
0.285
AC:
43338
AN:
151802
Hom.:
6609
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.239
Gnomad AMI
AF:
0.209
Gnomad AMR
AF:
0.313
Gnomad ASJ
AF:
0.237
Gnomad EAS
AF:
0.587
Gnomad SAS
AF:
0.424
Gnomad FIN
AF:
0.350
Gnomad MID
AF:
0.228
Gnomad NFE
AF:
0.269
Gnomad OTH
AF:
0.263
GnomAD4 exome
AF:
0.315
AC:
51
AN:
162
Hom.:
13
AF XY:
0.260
AC XY:
27
AN XY:
104
show subpopulations
Gnomad4 AFR exome
AF:
0.500
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.500
Gnomad4 EAS exome
AF:
0.714
Gnomad4 FIN exome
AF:
0.500
Gnomad4 NFE exome
AF:
0.226
Gnomad4 OTH exome
AF:
0.375
GnomAD4 genome
AF:
0.285
AC:
43352
AN:
151920
Hom.:
6612
Cov.:
31
AF XY:
0.295
AC XY:
21872
AN XY:
74240
show subpopulations
Gnomad4 AFR
AF:
0.239
Gnomad4 AMR
AF:
0.313
Gnomad4 ASJ
AF:
0.237
Gnomad4 EAS
AF:
0.587
Gnomad4 SAS
AF:
0.423
Gnomad4 FIN
AF:
0.350
Gnomad4 NFE
AF:
0.269
Gnomad4 OTH
AF:
0.263
Alfa
AF:
0.270
Hom.:
9313
Bravo
AF:
0.280
Asia WGS
AF:
0.486
AC:
1686
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
2.0
DANN
Benign
0.83

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.

Other links and lift over

dbSNP: rs3785817; hg19: chr17-42423665; API