Variant chr17-44907331-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002055.5(GFAP):c.*16G>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 0.0307 in 1,612,176 control chromosomes in the GnomAD database, including 880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 61 hom., cov: 32)

Exomes 𝑓: 0.031 ( 819 hom. )

Consequence

GFAP
NM_002055.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.410

Variant links:

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]

GFAP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 17-44907331-C-T is Benign according to our data. Variant chr17-44907331-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 323608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0237 (3602/152198) while in subpopulation NFE AF= 0.0374 (2542/67988). AF 95% confidence interval is 0.0362. There are 61 homozygotes in gnomad4. There are 1726 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3602 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFAP	NM_002055.5 linkuse as main transcript	c.*16G>A		3_prime_UTR_variant	9/9	ENST00000588735.3	NP_002046.1
GFAP	NM_001363846.2 linkuse as main transcript	c.*16G>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 linkuse as main transcript	c.*16G>A		3_prime_UTR_variant	9/9	1	NM_002055.5	ENSP00000466598	P1	P14136-1

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

3603

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00580

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0174

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00870

Gnomad FIN

AF:

0.0402

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0374

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0238

AC:

5977

AN:

251214

Hom.:

AF XY:

0.0239

AC XY:

3244

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00523

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00977

Gnomad FIN exome

AF:

0.0403

Gnomad NFE exome

AF:

0.0354

Gnomad OTH exome

AF:

0.0258

GnomAD4 exome

AF:

0.0314

AC:

45879

AN:

1459978

Hom.:

819

Cov.:

AF XY:

0.0310

AC XY:

22536

AN XY:

726416

show subpopulations

Gnomad4 AFR exome

AF:

0.00526

Gnomad4 AMR exome

AF:

0.0133

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00973

Gnomad4 FIN exome

AF:

0.0394

Gnomad4 NFE exome

AF:

0.0363

Gnomad4 OTH exome

AF:

0.0255

GnomAD4 genome

AF:

0.0237

AC:

3602

AN:

152198

Hom.:

Cov.:

AF XY:

0.0232

AC XY:

1726

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00578

Gnomad4 AMR

AF:

0.0174

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00871

Gnomad4 FIN

AF:

0.0402

Gnomad4 NFE

AF:

0.0374

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0326

Hom.:

Bravo

AF:

0.0208

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 30, 2016	- -

Alexander disease

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

-0.69

CADD

Benign

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over