17-44905727-G-A

Position:

• chr17-44905727-G-A

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.*1620C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 156,562 control chromosomes in the GnomAD database, including 913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (886 hom., cov: 33)
  • Exomes 𝑓: 0.099 (27 hom.)
• Consequence: GFAP NM_002055.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.328

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=-0.66).
• BP6: Variant 17-44905727-G-A is Benign according to our data. Variant chr17-44905727-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 369148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFAP	NM_002055.5	c.*1620C>T		3_prime_UTR_variant	9/9	ENST00000588735.3
GFAP	NM_001363846.2	c.*1620C>T		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFAP	ENST00000588735.3	c.*1620C>T		3_prime_UTR_variant	9/9	1	NM_002055.5	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16370 AN: 152114 Hom.: 888 Cov.: 33

Gnomad AFR AF: 0.0954

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.0986 AC: 427 AN: 4330 Hom.: 27 Cov.: 0 AF XY: 0.100 AC XY: 296 AN XY: 2950

Gnomad4 AFR exome AF: 0.0658

Gnomad4 AMR exome AF: 0.0543

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0735

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0667

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.108 AC: 16370 AN: 152232 Hom.: 886 Cov.: 33 AF XY: 0.106 AC XY: 7856 AN XY: 74436

Gnomad4 AFR AF: 0.0953

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0897

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0852

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.130

Alfa AF: 0.109 Hom.: 136

Bravo AF: 0.109

Asia WGS AF: 0.102 AC: 356 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.5
DANN	Benign	0.79

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: rs7049; hg19: chr17-42983095;