X-148885517-C-A

Position:

• chrX-148885517-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002025.4(AFF2):​c.1263-372C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.73 (23616 hom., 23467 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: AFF2 NM_002025.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFF2	NM_002025.4	c.1263-372C>A		intron_variant		ENST00000370460.7	NP_002016.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFF2	ENST00000370460.7	c.1263-372C>A		intron_variant		5	NM_002025.4	ENSP00000359489	P1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 79714 AN: 109594 Hom.: 23628 Cov.: 22 AF XY: 0.735 AC XY: 23450 AN XY: 31894

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.857

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.773

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.727 AC: 79715 AN: 109653 Hom.: 23616 Cov.: 22 AF XY: 0.734 AC XY: 23467 AN XY: 31963

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.900

Gnomad4 NFE AF: 0.916

Gnomad4 OTH AF: 0.772

Alfa AF: 0.734 Hom.: 7057

Bravo AF: 0.707

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.77

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: rs758440; hg19: chrX-147967047;