chr17-44346188-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002087.4(GRN):​c.-8+854C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 154,108 control chromosomes in the GnomAD database, including 6,409 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 0.28 ( 6284 hom., cov: 32)
Exomes 𝑓: 0.32 ( 125 hom. )

Consequence

GRN
NM_002087.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.620
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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRNNM_002087.4 linkc.-8+854C>T intron_variant Intron 1 of 12 ENST00000053867.8 NP_002078.1 P28799-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRNENST00000053867.8 linkc.-8+854C>T intron_variant Intron 1 of 12 1 NM_002087.4 ENSP00000053867.2 P28799-1

Frequencies

GnomAD3 genomes
AF:
0.277
AC:
42115
AN:
151948
Hom.:
6280
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.233
Gnomad AMI
AF:
0.209
Gnomad AMR
AF:
0.309
Gnomad ASJ
AF:
0.237
Gnomad EAS
AF:
0.583
Gnomad SAS
AF:
0.430
Gnomad FIN
AF:
0.328
Gnomad MID
AF:
0.218
Gnomad NFE
AF:
0.259
Gnomad OTH
AF:
0.258
GnomAD4 exome
AF:
0.322
AC:
657
AN:
2042
Hom.:
125
Cov.:
0
AF XY:
0.315
AC XY:
354
AN XY:
1124
show subpopulations
Gnomad4 AFR exome
AF:
0.250
AC:
10
AN:
40
Gnomad4 AMR exome
AF:
0.393
AC:
11
AN:
28
Gnomad4 ASJ exome
AF:
0.260
AC:
13
AN:
50
Gnomad4 EAS exome
AF:
0.660
AC:
165
AN:
250
Gnomad4 SAS exome
AF:
0.563
AC:
9
AN:
16
Gnomad4 FIN exome
AF:
0.367
AC:
105
AN:
286
Gnomad4 NFE exome
AF:
0.252
AC:
316
AN:
1254
Gnomad4 Remaining exome
AF:
0.240
AC:
25
AN:
104
Heterozygous variant carriers
0
17
34
51
68
85
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.277
AC:
42131
AN:
152066
Hom.:
6284
Cov.:
32
AF XY:
0.287
AC XY:
21298
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.233
AC:
0.233317
AN:
0.233317
Gnomad4 AMR
AF:
0.309
AC:
0.308648
AN:
0.308648
Gnomad4 ASJ
AF:
0.237
AC:
0.237161
AN:
0.237161
Gnomad4 EAS
AF:
0.584
AC:
0.583721
AN:
0.583721
Gnomad4 SAS
AF:
0.429
AC:
0.428661
AN:
0.428661
Gnomad4 FIN
AF:
0.328
AC:
0.328069
AN:
0.328069
Gnomad4 NFE
AF:
0.259
AC:
0.258536
AN:
0.258536
Gnomad4 OTH
AF:
0.258
AC:
0.257576
AN:
0.257576
Heterozygous variant carriers
0
1509
3018
4527
6036
7545
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
446
892
1338
1784
2230
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.154
Hom.:
324
Bravo
AF:
0.273
Asia WGS
AF:
0.492
AC:
1710
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
6.1
DANN
Benign
0.94
Mutation Taster
=100/0
polymorphism (auto)

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: rs2879096; hg19: chr17-42423556; API