rs13402289

Variant names:

• chr2-100042927-C-T
• rs13402289
• NM_001386135.1:c.54-33995G>A

Variant summary

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

The NM_001386135.1(AFF3):​c.54-33995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,918 control chromosomes in the GnomAD database, including 2,211 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 0.16 (2211 hom., cov: 32)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 7 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386135.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFF3	NM_001386135.1	MANE Select	c.54-33995G>A		intron	N/A	NP_001373064.1	P51826-1
	AFF3	NM_001025108.2		c.54-31356G>A		intron	N/A	NP_001020279.1	P51826-2
	AFF3	NM_002285.3		c.54-33995G>A		intron	N/A	NP_002276.2	P51826-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFF3	ENST00000672756.2	MANE Select	c.54-33995G>A		intron	N/A	ENSP00000500419.1	P51826-1
	AFF3	ENST00000409579.5	TSL:5	c.54-31356G>A		intron	N/A	ENSP00000386834.1	P51826-2
	AFF3	ENST00000317233.8	TSL:5	c.54-33995G>A		intron	N/A	ENSP00000317421.4	P51826-1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24819 AN: 151800 Hom.: 2206 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.164 AC: 24851 AN: 151918 Hom.: 2211 Cov.: 32 AF XY: 0.164 AC XY: 12175 AN XY: 74230

African (AFR) AF: 0.0946 AC: 3921 AN: 41462

American (AMR) AF: 0.187 AC: 2859 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3462

East Asian (EAS) AF: 0.286 AC: 1472 AN: 5152

South Asian (SAS) AF: 0.210 AC: 1010 AN: 4810

European-Finnish (FIN) AF: 0.165 AC: 1737 AN: 10524

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12590 AN: 67924

Other (OTH) AF: 0.175 AC: 368 AN: 2108

Alfa AF: 0.172 Hom.: 786

Bravo AF: 0.164

Asia WGS AF: 0.215 AC: 744 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.69
PhyloP100		0.063
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13402289; hg19: chr2-100659389;