NM_001386135.1:c.54-39291C>T

Variant names:

• chr2-100048223-G-A
• rs17352801
• NM_001386135.1:c.54-39291C>T

Variant summary

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

The NM_001386135.1(AFF3):​c.54-39291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,208 control chromosomes in the GnomAD database, including 1,079 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 0.10 (1079 hom., cov: 33)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 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.54-39291C>T		intron	N/A	NP_001373064.1
	AFF3	NM_001025108.2		c.54-36652C>T		intron	N/A	NP_001020279.1
	AFF3	NM_002285.3		c.54-39291C>T		intron	N/A	NP_002276.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFF3	ENST00000672756.2	MANE Select	c.54-39291C>T		intron	N/A	ENSP00000500419.1
	AFF3	ENST00000409579.5	TSL:5	c.54-36652C>T		intron	N/A	ENSP00000386834.1
	AFF3	ENST00000317233.8	TSL:5	c.54-39291C>T		intron	N/A	ENSP00000317421.4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15286 AN: 152090 Hom.: 1079 Cov.: 33

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.0736

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

GnomAD4 genome AF: 0.100 AC: 15287 AN: 152208 Hom.: 1079 Cov.: 33 AF XY: 0.102 AC XY: 7559 AN XY: 74406

African (AFR) AF: 0.0388 AC: 1609 AN: 41520

American (AMR) AF: 0.0598 AC: 915 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0723 AC: 349 AN: 4826

European-Finnish (FIN) AF: 0.216 AC: 2284 AN: 10572

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9838 AN: 68020

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.0779 Hom.: 170

Bravo AF: 0.0837

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.0
DANN	Benign	0.55
PhyloP100		1.2
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: rs17352801; hg19: chr2-100664685;