17-44906346-C-T

Position:

• chr17-44906346-C-T

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.*1001G>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 0.108 in 152,590 control chromosomes in the GnomAD database, including 890 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 (888 hom., cov: 32)
  • Exomes 𝑓: 0.12 (2 hom.)
• Consequence: GFAP NM_002055.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.873

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=-0.83).
• BP6: Variant 17-44906346-C-T is Benign according to our data. Variant chr17-44906346-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 369152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFAP	NM_002055.5	c.*1001G>A		3_prime_UTR_variant	9/9	ENST00000588735.3	NP_002046.1
GFAP	NM_001363846.2	c.*1001G>A		3_prime_UTR_variant	10/10		NP_001350775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFAP	ENST00000588735.3	c.*1001G>A		3_prime_UTR_variant	9/9	1	NM_002055.5	ENSP00000466598	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16371 AN: 152026 Hom.: 890 Cov.: 32

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0853

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.121 AC: 54 AN: 446 Hom.: 2 Cov.: 0 AF XY: 0.118 AC XY: 34 AN XY: 288

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0658

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.108 AC: 16371 AN: 152144 Hom.: 888 Cov.: 32 AF XY: 0.106 AC XY: 7852 AN XY: 74370

Gnomad4 AFR AF: 0.0951

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0853

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.130

Alfa AF: 0.113 Hom.: 307

Bravo AF: 0.109

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.5
DANN	Benign	0.52

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: rs1042329; hg19: chr17-42983714;