rs17629022

Positions:

• chr17-44914681-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002055.5(GFAP):​c.461+345A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 330,546 control chromosomes in the GnomAD database, including 7,648 homozygotes. 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: 𝑓 0.21 (3468 hom., cov: 32)
  • Exomes 𝑓: 0.20 (4180 hom.)
• Consequence: GFAP NM_002055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFAP	NM_002055.5	c.461+345A>G		intron_variant		ENST00000588735.3
GFAP	NM_001131019.3	c.461+345A>G		intron_variant
GFAP	NM_001242376.3	c.461+345A>G		intron_variant
GFAP	NM_001363846.2	c.461+345A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFAP	ENST00000588735.3	c.461+345A>G		intron_variant		1	NM_002055.5	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32033 AN: 152012 Hom.: 3464 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.205 AC: 36542 AN: 178416 Hom.: 4180 Cov.: 0 AF XY: 0.207 AC XY: 19342 AN XY: 93566

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.0950

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.211 AC: 32054 AN: 152130 Hom.: 3468 Cov.: 32 AF XY: 0.208 AC XY: 15439 AN XY: 74378

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0864

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.217

Alfa AF: 0.215 Hom.: 2080

Bravo AF: 0.207

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.40
DANN	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs17629022; hg19: chr17-42992049;