rs1372589

chrX-148803143-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.1042-6733T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 110,838 control chromosomes in the GnomAD database, including 461 homozygotes. There are 1,824 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 0.063 (461 hom., 1824 hem., cov: 22)
• Consequence: AFF2 NM_002025.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFF2	NM_002025.4	c.1042-6733T>C		intron_variant		ENST00000370460.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFF2	ENST00000370460.7	c.1042-6733T>C		intron_variant		5	NM_002025.4	P1

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 6935 AN: 110785 Hom.: 458 Cov.: 22 AF XY: 0.0552 AC XY: 1825 AN XY: 33055

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0250

Gnomad EAS AF: 0.00254

Gnomad SAS AF: 0.00494

Gnomad FIN AF: 0.000668

Gnomad MID AF: 0.0464

Gnomad NFE AF: 0.00679

Gnomad OTH AF: 0.0637

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

GnomAD4 genome AF: 0.0626 AC: 6942 AN: 110838 Hom.: 461 Cov.: 22 AF XY: 0.0551 AC XY: 1824 AN XY: 33118

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0431

Gnomad4 ASJ AF: 0.0250

Gnomad4 EAS AF: 0.00255

Gnomad4 SAS AF: 0.00496

Gnomad4 FIN AF: 0.000668

Gnomad4 NFE AF: 0.00679

Gnomad4 OTH AF: 0.0628

Alfa AF: 0.0420 Hom.: 213

Bravo AF: 0.0753

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	9.3
Dann	Benign	0.82

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: rs1372589; hg19: chrX-147884667;