Variant 17-44907319-G-C 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_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

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4O: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]

GFAP 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=-0.81).

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 rank	MANE	Protein	UniProt
GFAP	NM_002055.5 link	c.*28C>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000588735.3	NP_002046.1	P14136-1
GFAP	NM_001363846.2 link	c.*28C>G		3_prime_UTR_variant	Exon 10 of 10		NP_001350775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFAP	ENST00000588735 link	c.*28C>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_002055.5	ENSP00000466598.2		P14136-1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39671

AN:

151828

Hom.:

5263

Cov.:

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.:

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.:

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:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29746255) -

Oct 23, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Epithelial Biology; Institute of Medical Biology, Singapore

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary ciliary dyskinesia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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.

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