17-44907319-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002055.5(GFAP):c.*28C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,607,022 control chromosomes in the GnomAD database, including 59,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5268 hom., cov: 31)
  • Exomes 𝑓: 0.27 (54407 hom.)
• Consequence: GFAP NM_002055.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: 0.866

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-44907319-G-C is Benign according to our data. Variant chr17-44907319-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 66424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFAP	NM_002055.5	c.*28C>G		3_prime_UTR_variant	9/9	ENST00000588735.3
GFAP	NM_001363846.2	c.*28C>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFAP	ENST00000588735.3	c.*28C>G		3_prime_UTR_variant	9/9	1	NM_002055.5	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39671 AN: 151828 Hom.: 5263 Cov.: 31

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.264

GnomAD3 exomes AF: 0.268 AC: 67169 AN: 250892 Hom.: 9232 AF XY: 0.268 AC XY: 36398 AN XY: 135626

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.254

Gnomad SAS exome AF: 0.283

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.276

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.272 AC: 395845 AN: 1455076 Hom.: 54407 Cov.: 30 AF XY: 0.273 AC XY: 197643 AN XY: 724252

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.261 AC: 39698 AN: 151946 Hom.: 5268 Cov.: 31 AF XY: 0.261 AC XY: 19367 AN XY: 74252

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.262

Alfa AF: 0.205 Hom.: 670

Bravo AF: 0.252

Asia WGS AF: 0.228 AC: 790 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2 Other:1

not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 23, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 29746255) -

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.0
Dann	Benign	0.73

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: rs11558961; hg19: chr17-42984687; COSMIC: COSV53652894; COSMIC: COSV53652894;