rs17023158

chr2-99831464-T-C

Variant summary

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

The NM_001386135.1(AFF3):c.921+6013A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 152,282 control chromosomes in the GnomAD database, including 141 homozygotes. 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 0.034 (141 hom., cov: 33)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

Genes affected

AFF3 (HGNC:6473): (ALF transcription elongation factor 3) This gene encodes a tissue-restricted nuclear transcriptional activator that is preferentially expressed in lymphoid tissue. Isolation of this protein initially defined a highly conserved LAF4/MLLT2 gene family of nuclear transcription factors that may function in lymphoid development and oncogenesis. In some ALL patients, this gene has been found fused to the gene for MLL. Multiple alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFF3	NM_001386135.1	c.921+6013A>G		intron_variant		ENST00000672756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFF3	ENST00000672756.2	c.921+6013A>G		intron_variant			NM_001386135.1	A2

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5247 AN: 152164 Hom.: 141 Cov.: 33

Gnomad AFR AF: 0.00970

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0634

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.0605

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0377

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

GnomAD4 genome AF: 0.0345 AC: 5251 AN: 152282 Hom.: 141 Cov.: 33 AF XY: 0.0362 AC XY: 2697 AN XY: 74460

Gnomad4 AFR AF: 0.00967

Gnomad4 AMR AF: 0.0635

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.0635

Gnomad4 SAS AF: 0.0605

Gnomad4 FIN AF: 0.0458

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.0373

Alfa AF: 0.0396 Hom.: 121

Bravo AF: 0.0341

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.15
Dann	Benign	0.42

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: rs17023158; hg19: chr2-100447926;