rs6641482

chrX-148998565-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
AFF2	NM_002025.4	c.*7233A>G		3_prime_UTR_variant	21/21	ENST00000370460.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFF2	ENST00000370460.7	c.*7233A>G		3_prime_UTR_variant	21/21	5	NM_002025.4	P1
AFF2	ENST00000286437.7	c.*7233A>G		3_prime_UTR_variant	18/18	2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 13135 AN: 111023 Hom.: 681 Cov.: 23 AF XY: 0.107 AC XY: 3550 AN XY: 33237

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: 16 AN: 305 Hom.: 0 Cov.: 0 AF XY: 0.0752 AC XY: 10 AN XY: 133

Gnomad4 FIN exome AF: 0.0537

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.118 AC: 13138 AN: 111081 Hom.: 682 Cov.: 23 AF XY: 0.107 AC XY: 3551 AN XY: 33305

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.0729

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0231

Gnomad4 SAS AF: 0.0517

Gnomad4 FIN AF: 0.0692

Gnomad4 NFE AF: 0.0991

Gnomad4 OTH AF: 0.107

Alfa AF: 0.103 Hom.: 6830

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
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6641482; hg19: chrX-148080095; COSMIC: COSV54012824; COSMIC: COSV54012824;