dbSNP rs6641482: AFF2:c.*7233A>G (chrX-148998565-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002025.4(AFF2):c.*7233A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 111,386 control chromosomes in the GnomAD database, including 682 homozygotes. There are 3,561 hemizygotes in GnomAD. 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 0.12 ( 682 hom., 3551 hem., cov: 23)

Exomes 𝑓: 0.052 ( 0 hom. 10 hem. )

Consequence

AFF2
NM_002025.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.592

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

FRAXE intellectual disability
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

AFF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFF2	NM_002025.4 link	c.*7233A>G		3_prime_UTR_variant	Exon 21 of 21	ENST00000370460.7	NP_002016.2	P51816-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFF2	ENST00000370460.7 link	c.*7233A>G		3_prime_UTR_variant	Exon 21 of 21	5	NM_002025.4	ENSP00000359489.2		P51816-1
AFF2	ENST00000286437.7 link	c.*7233A>G		3_prime_UTR_variant	Exon 18 of 18	2		ENSP00000286437.5		P51816-7

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

13135

AN:

111023

Hom.:

681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.0733

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.0230

Gnomad SAS

AF:

0.0523

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.0681

Gnomad NFE

AF:

0.0992

Gnomad OTH

AF:

0.106

GnomAD4 exome

AF:

0.0525

AC:

AN:

305

Hom.:

Cov.:

AF XY:

0.0752

AC XY:

AN XY:

133

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0537

AC:

AN:

298

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.118

AC:

13138

AN:

111081

Hom.:

682

Cov.:

AF XY:

0.107

AC XY:

3551

AN XY:

33305

show subpopulations

African (AFR)

AF:

0.190

AC:

5779

AN:

30433

American (AMR)

AF:

0.0729

AC:

764

AN:

10479

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

320

AN:

2643

East Asian (EAS)

AF:

0.0231

AC:

AN:

3551

South Asian (SAS)

AF:

0.0517

AC:

135

AN:

2612

European-Finnish (FIN)

AF:

0.0692

AC:

415

AN:

6001

Middle Eastern (MID)

AF:

0.0698

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0991

AC:

5249

AN:

52949

Other (OTH)

AF:

0.107

AC:

163

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

423

846

1268

1691

2114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.108

Hom.:

10332

Bravo

AF:

0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.4

(source)

DANN

Benign

0.79

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over