rs13385193

Variant names:

• chr2-99982945-T-C
• rs13385193
• NM_001386135.1:c.873+23687A>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.873+23687A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,074 control chromosomes in the GnomAD database, including 4,068 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 0.21 (4068 hom., cov: 32)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 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.873+23687A>G		intron	N/A	NP_001373064.1
	AFF3	NM_001025108.2		c.948+23687A>G		intron	N/A	NP_001020279.1
	AFF3	NM_002285.3		c.873+23687A>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.873+23687A>G		intron	N/A	ENSP00000500419.1
	AFF3	ENST00000409579.5	TSL:5	c.948+23687A>G		intron	N/A	ENSP00000386834.1
	AFF3	ENST00000317233.8	TSL:5	c.873+23687A>G		intron	N/A	ENSP00000317421.4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31219 AN: 151956 Hom.: 4055 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.206 AC: 31265 AN: 152074 Hom.: 4068 Cov.: 32 AF XY: 0.203 AC XY: 15102 AN XY: 74356

African (AFR) AF: 0.355 AC: 14729 AN: 41434

American (AMR) AF: 0.107 AC: 1642 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 315 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0915 AC: 441 AN: 4820

European-Finnish (FIN) AF: 0.233 AC: 2462 AN: 10568

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11294 AN: 67994

Other (OTH) AF: 0.159 AC: 336 AN: 2114

Alfa AF: 0.171 Hom.: 1334

Bravo AF: 0.201

Asia WGS AF: 0.0600 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.073
DANN	Benign	0.51
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: rs13385193; hg19: chr2-100599407;