rs3744470

chr17-44906533-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002055.5(GFAP):c.*814T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,462 control chromosomes in the GnomAD database, including 1,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1226 hom., cov: 32)
  • Exomes 𝑓: 0.097 (3 hom.)
• Consequence: GFAP NM_002055.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.190

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-44906533-A-T is Benign according to our data. Variant chr17-44906533-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 323601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFAP	NM_002055.5	c.*814T>A		3_prime_UTR_variant	9/9	ENST00000588735.3
GFAP	NM_001363846.2	c.*814T>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFAP	ENST00000588735.3	c.*814T>A		3_prime_UTR_variant	9/9	1	NM_002055.5	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18583 AN: 151964 Hom.: 1225 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.0974 AC: 37 AN: 380 Hom.: 3 Cov.: 0 AF XY: 0.0938 AC XY: 18 AN XY: 192

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.0909

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.122 AC: 18599 AN: 152082 Hom.: 1226 Cov.: 32 AF XY: 0.125 AC XY: 9283 AN XY: 74356

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0448 Hom.: 53

Bravo AF: 0.121

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.5
Dann	Benign	0.57

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: rs3744470; hg19: chr17-42983901;