rs11676922

Variant names:

• chr2-100190478-T-A
• rs11676922
• ENST00000672999.1:n.287+1664A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-100190478-T-A
• chr2-100190478-T-C
• chr2-100190478-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000672999.1(AFF3):​n.287+1664A>T variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 45 publications found

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]

AFF3 Gene-Disease associations (from GenCC):

• KINSSHIP syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• intellectual disability

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFF3	ENST00000672999.1	n.287+1664A>T		intron_variant	Intron 1 of 4

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

African (AFR) AF: 0.466 AC: 19349 AN: 41480

American (AMR) AF: 0.430 AC: 6569 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1883 AN: 3470

East Asian (EAS) AF: 0.613 AC: 3168 AN: 5172

South Asian (SAS) AF: 0.437 AC: 2106 AN: 4816

European-Finnish (FIN) AF: 0.552 AC: 5831 AN: 10566

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36649 AN: 67988

Other (OTH) AF: 0.505 AC: 1068 AN: 2114

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
PhyloP100		-0.050

Splicing

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

Other links and lift over

dbSNP: rs11676922; hg19: chr2-100806940;