rs17023516

chr2-100120188-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.-145+9036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,246 control chromosomes in the GnomAD database, including 1,210 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 0.11 (1210 hom., cov: 32)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFF3	NM_001386135.1	c.-145+9036A>G		intron_variant		ENST00000672756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFF3	ENST00000672756.2	c.-145+9036A>G		intron_variant			NM_001386135.1	A2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17383 AN: 152128 Hom.: 1210 Cov.: 32

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.114 AC: 17381 AN: 152246 Hom.: 1210 Cov.: 32 AF XY: 0.114 AC XY: 8467 AN XY: 74440

Gnomad4 AFR AF: 0.0981

Gnomad4 AMR AF: 0.0588

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0818

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.128 Hom.: 684

Bravo AF: 0.101

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.1
Dann	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17023516; hg19: chr2-100736650;