Variant 17-44910156-T-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.1171+459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,613,168 control chromosomes in the GnomAD database, including 59,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5268 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54618 hom. )

Consequence

GFAP
NM_002055.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.401

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 (MetaRNN=0.0044329464).

BP6

Variant 17-44910156-T-C is Benign according to our data. Variant chr17-44910156-T-C is described in ClinVar as [Benign]. Clinvar id is 1164603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-44910156-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GFAP	NM_002055.5 linkuse as main transcript	c.1171+459A>G		intron_variant		ENST00000588735.3
GFAP	NM_001363846.2 linkuse as main transcript	c.1276A>G	p.Thr426Ala	missense_variant	8/10
GFAP	NM_001131019.3 linkuse as main transcript	c.1276A>G	p.Thr426Ala	missense_variant	8/8
GFAP	NM_001242376.3 linkuse as main transcript	c.*313A>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFAP	ENST00000588735.3 linkuse as main transcript	c.1171+459A>G		intron_variant		1	NM_002055.5	P1	P14136-1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39704

AN:

151990

Hom.:

5263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.264

GnomAD3 exomes

AF:

0.268

AC:

66759

AN:

248826

Hom.:

9227

AF XY:

0.269

AC XY:

36365

AN XY:

135216

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:

0.282

Gnomad FIN exome

AF:

0.322

Gnomad NFE exome

AF:

0.277

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.273

AC:

398413

AN:

1461060

Hom.:

54618

Cov.:

AF XY:

0.273

AC XY:

198762

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.225

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.219

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.316

Gnomad4 NFE exome

AF:

0.276

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.261

AC:

39731

AN:

152108

Hom.:

5268

Cov.:

AF XY:

0.261

AC XY:

19394

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.227

Gnomad4 ASJ

AF:

0.242

Gnomad4 EAS

AF:

0.253

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.318

Gnomad4 NFE

AF:

0.280

Gnomad4 OTH

AF:

0.261

Alfa

AF:

0.270

Hom.:

8882

Bravo

AF:

0.253

TwinsUK

AF:

0.259

AC:

960

ALSPAC

AF:

0.260

AC:

1003

ESP6500AA

AF:

0.241

AC:

756

ESP6500EA

AF:

0.274

AC:

1965

ExAC

AF:

0.267

AC:

32176

Asia WGS

AF:

0.228

AC:

790

AN:

3478

EpiCase

AF:

0.270

EpiControl

AF:

0.261

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.20

T;T

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P

PROVEAN

Benign

-0.41

.;N

REVEL

Benign

0.16

Sift

Benign

0.14

.;T

Sift4G

Benign

0.22

.;T

Vest4

0.040

ClinPred

0.0012

GERP RS

3.8

gMVP

0.26

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