X-148803846-T-C

Position:

• chrX-148803846-T-C

Variant summary

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

The NM_002025.4(AFF2):​c.1042-6030T>C 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 0.77 (22900 hom., 23121 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: AFF2 NM_002025.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544

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=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFF2	NM_002025.4	c.1042-6030T>C		intron_variant		ENST00000370460.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFF2	ENST00000370460.7	c.1042-6030T>C		intron_variant		5	NM_002025.4	P1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 82537 AN: 107816 Hom.: 22905 Cov.: 21 AF XY: 0.763 AC XY: 23071 AN XY: 30218

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.866

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.815

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: 0.766 AC: 82577 AN: 107869 Hom.: 22900 Cov.: 21 AF XY: 0.764 AC XY: 23121 AN XY: 30281

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.871

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.815

Alfa AF: 0.754 Hom.: 10596

Bravo AF: 0.784

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.52

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: rs1860929; hg19: chrX-147885370;