chr17-44346188-C-T
Variant names:
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
NM_002087.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.620
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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.277 AC: 42115AN: 151948Hom.: 6280 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
42115
AN:
151948
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.322 AC: 657AN: 2042Hom.: 125 Cov.: 0 AF XY: 0.315 AC XY: 354AN XY: 1124 show subpopulations
GnomAD4 exome
AF:
AC:
657
AN:
2042
Hom.:
Cov.:
0
AF XY:
AC XY:
354
AN XY:
1124
Gnomad4 AFR exome
AF:
AC:
10
AN:
40
Gnomad4 AMR exome
AF:
AC:
11
AN:
28
Gnomad4 ASJ exome
AF:
AC:
13
AN:
50
Gnomad4 EAS exome
AF:
AC:
165
AN:
250
Gnomad4 SAS exome
AF:
AC:
9
AN:
16
Gnomad4 FIN exome
AF:
AC:
105
AN:
286
Gnomad4 NFE exome
AF:
AC:
316
AN:
1254
Gnomad4 Remaining exome
AF:
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: 42131AN: 152066Hom.: 6284 Cov.: 32 AF XY: 0.287 AC XY: 21298AN XY: 74324 show subpopulations
GnomAD4 genome
AF:
AC:
42131
AN:
152066
Hom.:
Cov.:
32
AF XY:
AC XY:
21298
AN XY:
74324
Gnomad4 AFR
AF:
AC:
0.233317
AN:
0.233317
Gnomad4 AMR
AF:
AC:
0.308648
AN:
0.308648
Gnomad4 ASJ
AF:
AC:
0.237161
AN:
0.237161
Gnomad4 EAS
AF:
AC:
0.583721
AN:
0.583721
Gnomad4 SAS
AF:
AC:
0.428661
AN:
0.428661
Gnomad4 FIN
AF:
AC:
0.328069
AN:
0.328069
Gnomad4 NFE
AF:
AC:
0.258536
AN:
0.258536
Gnomad4 OTH
AF:
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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1710
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
Mutation Taster
=100/0
polymorphism (auto)
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at