rs17318101

Positions:

• chrX-148636091-T-C

Variant summary

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

The NM_002025.4(AFF2):​c.48-15908T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 110,424 control chromosomes in the GnomAD database, including 1,246 homozygotes. There are 5,486 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 0.17 (1246 hom., 5486 hem., cov: 22)
• Consequence: AFF2 NM_002025.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.892

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=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFF2	NM_002025.4	c.48-15908T>C		intron_variant		ENST00000370460.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFF2	ENST00000370460.7	c.48-15908T>C		intron_variant		5	NM_002025.4	P1
AFF2	ENST00000342251.7	c.48-15908T>C		intron_variant		1
AFF2	ENST00000370457.9	c.48-15908T>C		intron_variant		1
AFF2	ENST00000370458.5	c.48-15908T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 19117 AN: 110378 Hom.: 1246 Cov.: 22 AF XY: 0.168 AC XY: 5491 AN XY: 32616

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.00480

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.129

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.173 AC: 19112 AN: 110424 Hom.: 1246 Cov.: 22 AF XY: 0.168 AC XY: 5486 AN XY: 32672

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.00481

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.191

Alfa AF: 0.193 Hom.: 3549

Bravo AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs17318101; hg19: chrX-147717612;