rs11685258

Variant names:

• chr2-100065332-T-G
• rs11685258
• NM_001386135.1:c.53+39070A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001386135.1(AFF3):​c.53+39070A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,114 control chromosomes in the GnomAD database, including 1,684 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 0.13 (1684 hom., cov: 33)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFF3	NM_001386135.1	c.53+39070A>C		intron_variant	Intron 4 of 24	ENST00000672756.2	NP_001373064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFF3	ENST00000672756.2	c.53+39070A>C		intron_variant	Intron 4 of 24		NM_001386135.1	ENSP00000500419.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20138 AN: 151996 Hom.: 1683 Cov.: 33

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0745

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.132 AC: 20134 AN: 152114 Hom.: 1684 Cov.: 33 AF XY: 0.129 AC XY: 9615 AN XY: 74366

African (AFR) AF: 0.0404 AC: 1679 AN: 41516

American (AMR) AF: 0.131 AC: 1997 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1011 AN: 3468

East Asian (EAS) AF: 0.0747 AC: 387 AN: 5182

South Asian (SAS) AF: 0.200 AC: 964 AN: 4822

European-Finnish (FIN) AF: 0.0948 AC: 1004 AN: 10586

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12353 AN: 67936

Other (OTH) AF: 0.166 AC: 350 AN: 2114

Alfa AF: 0.150 Hom.: 252

Bravo AF: 0.130

Asia WGS AF: 0.141 AC: 491 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.85
PhyloP100		1.5
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: rs11685258; hg19: chr2-100681794; COSMIC: COSV57847326;