chr17-44907319-G-C

Variant summary

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

The NM_002055.5(GFAP):​c.*28C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,607,022 control chromosomes in the GnomAD database, including 59,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5268 hom., cov: 31)
Exomes 𝑓: 0.27 ( 54407 hom. )

Consequence

GFAP
NM_002055.5 3_prime_UTR

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.866
Variant links:
Genes affected
GFAP (HGNC:4235): (glial fibrillary acidic protein) This gene encodes one of the major intermediate filament proteins of mature astrocytes. It is used as a marker to distinguish astrocytes from other glial cells during development. Mutations in this gene cause Alexander disease, a rare disorder of astrocytes in the central nervous system. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 17-44907319-G-C is Benign according to our data. Variant chr17-44907319-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 66424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GFAPNM_002055.5 linkuse as main transcriptc.*28C>G 3_prime_UTR_variant 9/9 ENST00000588735.3
GFAPNM_001363846.2 linkuse as main transcriptc.*28C>G 3_prime_UTR_variant 10/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GFAPENST00000588735.3 linkuse as main transcriptc.*28C>G 3_prime_UTR_variant 9/91 NM_002055.5 P1P14136-1

Frequencies

GnomAD3 genomes
AF:
0.261
AC:
39671
AN:
151828
Hom.:
5263
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.231
Gnomad AMI
AF:
0.221
Gnomad AMR
AF:
0.226
Gnomad ASJ
AF:
0.241
Gnomad EAS
AF:
0.253
Gnomad SAS
AF:
0.272
Gnomad FIN
AF:
0.317
Gnomad MID
AF:
0.256
Gnomad NFE
AF:
0.280
Gnomad OTH
AF:
0.264
GnomAD3 exomes
AF:
0.268
AC:
67169
AN:
250892
Hom.:
9232
AF XY:
0.268
AC XY:
36398
AN XY:
135626
show subpopulations
Gnomad AFR exome
AF:
0.232
Gnomad AMR exome
AF:
0.224
Gnomad ASJ exome
AF:
0.245
Gnomad EAS exome
AF:
0.254
Gnomad SAS exome
AF:
0.283
Gnomad FIN exome
AF:
0.321
Gnomad NFE exome
AF:
0.276
Gnomad OTH exome
AF:
0.267
GnomAD4 exome
AF:
0.272
AC:
395845
AN:
1455076
Hom.:
54407
Cov.:
30
AF XY:
0.273
AC XY:
197643
AN XY:
724252
show subpopulations
Gnomad4 AFR exome
AF:
0.232
Gnomad4 AMR exome
AF:
0.225
Gnomad4 ASJ exome
AF:
0.238
Gnomad4 EAS exome
AF:
0.218
Gnomad4 SAS exome
AF:
0.283
Gnomad4 FIN exome
AF:
0.316
Gnomad4 NFE exome
AF:
0.275
Gnomad4 OTH exome
AF:
0.263
GnomAD4 genome
AF:
0.261
AC:
39698
AN:
151946
Hom.:
5268
Cov.:
31
AF XY:
0.261
AC XY:
19367
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.232
Gnomad4 AMR
AF:
0.226
Gnomad4 ASJ
AF:
0.241
Gnomad4 EAS
AF:
0.253
Gnomad4 SAS
AF:
0.272
Gnomad4 FIN
AF:
0.317
Gnomad4 NFE
AF:
0.280
Gnomad4 OTH
AF:
0.262
Alfa
AF:
0.205
Hom.:
670
Bravo
AF:
0.252
Asia WGS
AF:
0.228
AC:
790
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2Other:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015This variant is associated with the following publications: (PMID: 29746255) -
Benign, no assertion criteria providedclinical testingMayo Clinic Laboratories, Mayo ClinicOct 23, 2015- -
not provided, no classification providedliterature onlyEpithelial Biology; Institute of Medical Biology, Singapore-- -
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
8.0
DANN
Benign
0.73

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: rs11558961; hg19: chr17-42984687; COSMIC: COSV53652894; COSMIC: COSV53652894; API