rs797044584

Positions:

• chr17-44911313-C-CTGCAAG

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_002055.5(GFAP):​c.1049_1050insCTTGCA​(p.Tyr349_Gln350insHisLeu) variant causes a inframe insertion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GFAP NM_002055.5 inframe_insertion
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 8.02

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_002055.5.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFAP	NM_002055.5	c.1049_1050insCTTGCA	p.Tyr349_Gln350insHisLeu	inframe_insertion	6/9	ENST00000588735.3	NP_002046.1
GFAP	NM_001131019.3	c.1049_1050insCTTGCA	p.Tyr349_Gln350insHisLeu	inframe_insertion	6/8		NP_001124491.1
GFAP	NM_001242376.3	c.1049_1050insCTTGCA	p.Tyr349_Gln350insHisLeu	inframe_insertion	6/7		NP_001229305.1
GFAP	NM_001363846.2	c.1049_1050insCTTGCA	p.Tyr349_Gln350insHisLeu	inframe_insertion	6/10		NP_001350775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFAP	ENST00000588735.3	c.1049_1050insCTTGCA	p.Tyr349_Gln350insHisLeu	inframe_insertion	6/9	1	NM_002055.5	ENSP00000466598	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Alexander disease Other:1

not provided, no classification provided

literature only

GeneReviews

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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: rs797044584; hg19: chr17-42988681;