chrX-148983825-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002025.4(AFF2):​c.3623+3035G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.91 ( 32905 hom., 27013 hem., cov: 20)
Failed GnomAD Quality Control

Consequence

AFF2
NM_002025.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.918
Variant links:
Genes affected
AFF2 (HGNC:3776): (ALF transcription elongation factor 2) This gene encodes a putative transcriptional activator that is a member of the AF4\FMR2 gene family. This gene is associated with the folate-sensitive fragile X E locus on chromosome X. A repeat polymorphism in the fragile X E locus results in silencing of this gene causing Fragile X E syndrome. Fragile X E syndrome is a form of nonsyndromic X-linked cognitive disability. In addition, this gene contains 6-25 GCC repeats that are expanded to >200 repeats in the disease state. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jul 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AFF2NM_002025.4 linkuse as main transcriptc.3623+3035G>A intron_variant ENST00000370460.7 NP_002016.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AFF2ENST00000370460.7 linkuse as main transcriptc.3623+3035G>A intron_variant 5 NM_002025.4 ENSP00000359489 P1P51816-1

Frequencies

GnomAD3 genomes
AF:
0.914
AC:
97849
AN:
107071
Hom.:
32911
Cov.:
20
AF XY:
0.916
AC XY:
26969
AN XY:
29439
show subpopulations
Gnomad AFR
AF:
0.724
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.947
Gnomad ASJ
AF:
0.980
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
0.997
Gnomad FIN
AF:
0.998
Gnomad MID
AF:
0.952
Gnomad NFE
AF:
0.992
Gnomad OTH
AF:
0.915
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
0.914
AC:
97881
AN:
107119
Hom.:
32905
Cov.:
20
AF XY:
0.916
AC XY:
27013
AN XY:
29497
show subpopulations
Gnomad4 AFR
AF:
0.724
Gnomad4 AMR
AF:
0.947
Gnomad4 ASJ
AF:
0.980
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
0.999
Gnomad4 FIN
AF:
0.998
Gnomad4 NFE
AF:
0.992
Gnomad4 OTH
AF:
0.916
Alfa
AF:
0.962
Hom.:
17382
Bravo
AF:
0.903

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.11
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

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

Other links and lift over

dbSNP: rs1076374; hg19: chrX-148065355; API