2-100120188-T-C

Variant names:

• chr2-100120188-T-C
• rs17023516
• NM_001386135.1:c.-145+9036A>G

Variant summary

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

The NM_001386135.1(AFF3):​c.-145+9036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,246 control chromosomes in the GnomAD database, including 1,210 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 0.11 (1210 hom., cov: 32)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFF3	NM_001386135.1	MANE Select	c.-145+9036A>G		intron	N/A	NP_001373064.1
	AFF3	NM_002285.3		c.-144-14605A>G		intron	N/A	NP_002276.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFF3	ENST00000672756.2	MANE Select	c.-145+9036A>G		intron	N/A	ENSP00000500419.1
	AFF3	ENST00000317233.8	TSL:5	c.-144-14605A>G		intron	N/A	ENSP00000317421.4
	AFF3	ENST00000672204.1		c.-144-14605A>G		intron	N/A	ENSP00000500616.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17383 AN: 152128 Hom.: 1210 Cov.: 32

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.114 AC: 17381 AN: 152246 Hom.: 1210 Cov.: 32 AF XY: 0.114 AC XY: 8467 AN XY: 74440

African (AFR) AF: 0.0981 AC: 4078 AN: 41550

American (AMR) AF: 0.0588 AC: 900 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0818 AC: 395 AN: 4826

European-Finnish (FIN) AF: 0.204 AC: 2161 AN: 10592

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9521 AN: 68012

Other (OTH) AF: 0.0781 AC: 165 AN: 2114

Alfa AF: 0.128 Hom.: 745

Bravo AF: 0.101

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17023516; hg19: chr2-100736650;