rs11676922

chr2-100190478-T-Achr2-100190478-T-Cchr2-100190478-T-G

Variant summary

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

The ENST00000672999.1(AFF3):n.287+1664A>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,090 control chromosomes in the GnomAD database, including 19,913 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 0.51 (19913 hom., cov: 33)
• Consequence: AFF3 ENST00000672999.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFF3	ENST00000672999.1	n.287+1664A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77114 AN: 151972 Hom.: 19892 Cov.: 33

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.507 AC: 77184 AN: 152090 Hom.: 19913 Cov.: 33 AF XY: 0.506 AC XY: 37610 AN XY: 74358

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.505

Alfa AF: 0.519 Hom.: 2536

Bravo AF: 0.498

Asia WGS AF: 0.480 AC: 1666 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.5
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11676922; hg19: chr2-100806940;