17-44910144-G-T

Variant names:

• chr17-44910144-G-T
• NM_002055.5:c.1171+471C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001363846.2(GFAP):​c.1288C>A​(p.Arg430Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R430C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GFAP NM_001363846.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.96

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21261773).
• BP6: Variant 17-44910144-G-T is Benign according to our data. Variant chr17-44910144-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1962658.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFAP	NM_002055.5	c.1171+471C>A		intron_variant	Intron 7 of 8	ENST00000588735.3	NP_002046.1
GFAP	NM_001363846.2	c.1288C>A	p.Arg430Ser	missense_variant	Exon 8 of 10		NP_001350775.1
GFAP	NM_001131019.3	c.1288C>A	p.Arg430Ser	missense_variant	Exon 8 of 8		NP_001124491.1
GFAP	NM_001242376.3	c.*325C>A		3_prime_UTR_variant	Exon 7 of 7		NP_001229305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFAP	ENST00000588735.3	c.1171+471C>A		intron_variant	Intron 7 of 8	1	NM_002055.5	ENSP00000466598.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.97
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.39	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.76	T
PROVEAN	Benign	-0.68	.;N
REVEL	Benign	0.26
Sift	Uncertain	0.0050	.;D
Sift4G	Benign	0.14	.;T
Vest4		0.14
MutPred		0.25		Gain of glycosylation at R430 (P = 0.0018);Gain of glycosylation at R430 (P = 0.0018);
MVP		0.57
ClinPred		0.39	T
GERP RS		3.8
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-42987512;