Variant rs12011040 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002025.4(AFF2):c.1488G>A(p.Ser496=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 1,208,514 control chromosomes in the GnomAD database, including 4,114 homozygotes. There are 20,624 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1779 hom., 4175 hem., cov: 22)

Exomes 𝑓: 0.047 ( 2335 hom. 16449 hem. )

Consequence

AFF2
NM_002025.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -7.97

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]

AFF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant X-148953670-G-A is Benign according to our data. Variant chrX-148953670-G-A is described in ClinVar as [Benign]. Clinvar id is 128281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-148953670-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-7.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFF2	NM_002025.4 linkuse as main transcript	c.1488G>A	p.Ser496=	synonymous_variant	10/21	ENST00000370460.7	NP_002016.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFF2	ENST00000370460.7 linkuse as main transcript	c.1488G>A	p.Ser496=	synonymous_variant	10/21	5	NM_002025.4	ENSP00000359489	P1	P51816-1

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

15462

AN:

110754

Hom.:

1778

Cov.:

AF XY:

0.126

AC XY:

4159

AN XY:

33010

show subpopulations

Gnomad AFR

AF:

0.385

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.0667

Gnomad ASJ

AF:

0.0813

Gnomad EAS

AF:

0.00283

Gnomad SAS

AF:

0.0244

Gnomad FIN

AF:

0.0587

Gnomad MID

AF:

0.0805

Gnomad NFE

AF:

0.0419

Gnomad OTH

AF:

0.106

GnomAD3 exomes

AF:

0.0649

AC:

11878

AN:

182894

Hom.:

946

AF XY:

0.0556

AC XY:

3750

AN XY:

67416

show subpopulations

Gnomad AFR exome

AF:

0.405

Gnomad AMR exome

AF:

0.0287

Gnomad ASJ exome

AF:

0.0735

Gnomad EAS exome

AF:

0.00209

Gnomad SAS exome

AF:

0.0336

Gnomad FIN exome

AF:

0.0617

Gnomad NFE exome

AF:

0.0411

Gnomad OTH exome

AF:

0.0480

GnomAD4 exome

AF:

0.0472

AC:

51804

AN:

1097707

Hom.:

2335

Cov.:

AF XY:

0.0453

AC XY:

16449

AN XY:

363105

show subpopulations

Gnomad4 AFR exome

AF:

0.416

Gnomad4 AMR exome

AF:

0.0326

Gnomad4 ASJ exome

AF:

0.0741

Gnomad4 EAS exome

AF:

0.00113

Gnomad4 SAS exome

AF:

0.0336

Gnomad4 FIN exome

AF:

0.0629

Gnomad4 NFE exome

AF:

0.0365

Gnomad4 OTH exome

AF:

0.0621

GnomAD4 genome

AF:

0.140

AC:

15489

AN:

110807

Hom.:

1779

Cov.:

AF XY:

0.126

AC XY:

4175

AN XY:

33073

show subpopulations

Gnomad4 AFR

AF:

0.385

Gnomad4 AMR

AF:

0.0665

Gnomad4 ASJ

AF:

0.0813

Gnomad4 EAS

AF:

0.00284

Gnomad4 SAS

AF:

0.0245

Gnomad4 FIN

AF:

0.0587

Gnomad4 NFE

AF:

0.0419

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.0711

Hom.:

2113

Bravo

AF:

0.156

EpiCase

AF:

0.0398

EpiControl

AF:

0.0405

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 17, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 21, 2016	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

FRAXE

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.12

DANN

Benign

0.61

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