Variant chr17-44913439-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.619-9C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,613,650 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 31 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 181 hom. )

Consequence

GFAP
NM_002055.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.009794

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.42

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:

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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=-0.8).

BP6

Variant 17-44913439-G-C is Benign according to our data. Variant chr17-44913439-G-C is described in ClinVar as [Benign]. Clinvar id is 323617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
GFAP	NM_002055.5 linkuse as main transcript	c.619-9C>G	splice_polypyrimidine_tract_variant, intron_variant	ENST00000588735.3	NP_002046.1
GFAP	NM_001131019.3 linkuse as main transcript	c.619-9C>G	splice_polypyrimidine_tract_variant, intron_variant		NP_001124491.1
GFAP	NM_001242376.3 linkuse as main transcript	c.619-9C>G	splice_polypyrimidine_tract_variant, intron_variant		NP_001229305.1
GFAP	NM_001363846.2 linkuse as main transcript	c.619-9C>G	splice_polypyrimidine_tract_variant, intron_variant		NP_001350775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFAP	ENST00000588735.3 linkuse as main transcript	c.619-9C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002055.5	ENSP00000466598	P1	P14136-1

Frequencies

GnomAD3 genomes

AF:

0.00611

AC:

930

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0382

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.0459

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.0112

AC:

2796

AN:

250172

Hom.:

AF XY:

0.00931

AC XY:

1260

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.0520

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.0396

Gnomad SAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.00182

Gnomad NFE exome

AF:

0.000770

Gnomad OTH exome

AF:

0.00884

GnomAD4 exome

AF:

0.00413

AC:

6039

AN:

1461352

Hom.:

181

Cov.:

AF XY:

0.00392

AC XY:

2849

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0503

Gnomad4 ASJ exome

AF:

0.00348

Gnomad4 EAS exome

AF:

0.0688

Gnomad4 SAS exome

AF:

0.00220

Gnomad4 FIN exome

AF:

0.00231

Gnomad4 NFE exome

AF:

0.000310

Gnomad4 OTH exome

AF:

0.00504

GnomAD4 genome

AF:

0.00616

AC:

938

AN:

152298

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

553

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.0385

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.0456

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00207

Hom.:

Bravo

AF:

0.00784

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 18, 2017	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 16, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.9

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0098

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.020

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