dbSNP rs9916491: GFAP:n.2784A>T (chr17-44910156-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000591327.2(GFAP):n.2784A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GFAP
ENST00000591327.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.401

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Alexander disease
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
Alexander disease type II
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GFAP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.094138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFAP	NM_002055.5 link	c.1171+459A>T		intron_variant	Intron 7 of 8	ENST00000588735.3	NP_002046.1	P14136-1
GFAP	NM_001363846.2 link	c.1276A>T	p.Thr426Ser	missense_variant	Exon 8 of 10		NP_001350775.1
GFAP	NM_001131019.3 link	c.1276A>T	p.Thr426Ser	missense_variant	Exon 8 of 8		NP_001124491.1	P14136-3
GFAP	NM_001242376.3 link	c.*313A>T		3_prime_UTR_variant	Exon 7 of 7		NP_001229305.1	P14136-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFAP	ENST00000588735.3 link	c.1171+459A>T		intron_variant	Intron 7 of 8	1	NM_002055.5	ENSP00000466598.2		P14136-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461588

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111758

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.86

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.26

T;T

M_CAP

Benign

0.067

MetaRNN

Benign

0.094

T;T

MetaSVM

Benign

-0.81

PhyloP100

0.40

PROVEAN

Benign

1.3

.;N

REVEL

Benign

0.14

Sift

Benign

0.40

.;T

Sift4G

Benign

0.71

.;T

Vest4

0.090

MutPred

0.24

Gain of disorder (P = 0.0833);Gain of disorder (P = 0.0833);

MVP

0.69

ClinPred

0.042

GERP RS

3.8

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over