rs797044592

chr17-44910132-GCAGCTAAC-GGAT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The NM_002055.5(GFAP):c.1171+475_1171+482delinsATC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GFAP NM_002055.5 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP5: Variant 17-44910133-CAGCTAAC-GAT is Pathogenic according to our data. Variant chr17-44910133-CAGCTAAC-GAT is described in ClinVar as [Pathogenic]. Clinvar id is 190366.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFAP	NM_002055.5	c.1171+475_1171+482delinsATC		intron_variant		ENST00000588735.3
GFAP	NM_001131019.3	c.1292_*3delinsATC		stop_lost, 3_prime_UTR_variant	8/8
GFAP	NM_001242376.3	c.*329_*336delinsATC		3_prime_UTR_variant	7/7
GFAP	NM_001363846.2	c.1291+1_1291+8delinsATC		splice_donor_variant, splice_donor_5th_base_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFAP	ENST00000588735.3	c.1171+475_1171+482delinsATC		intron_variant		1	NM_002055.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Alexander disease Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

GeneReviews

Jan 08, 2015

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs797044592; hg19: chr17-42987501;