rs10199628

Variant names:

• chr2-100119394-T-C
• rs10199628
• NM_001386135.1:c.-145+9830A>G

Variant summary

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

The NM_001386135.1(AFF3):​c.-145+9830A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,188 control chromosomes in the GnomAD database, including 1,410 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 (1410 hom., cov: 32)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.911
• Publications: 1 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=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFF3	NM_001386135.1	c.-145+9830A>G		intron_variant	Intron 2 of 24	ENST00000672756.2	NP_001373064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFF3	ENST00000672756.2	c.-145+9830A>G		intron_variant	Intron 2 of 24		NM_001386135.1	ENSP00000500419.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19169 AN: 152070 Hom.: 1409 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0860

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.0908

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

GnomAD4 genome AF: 0.126 AC: 19171 AN: 152188 Hom.: 1410 Cov.: 32 AF XY: 0.125 AC XY: 9299 AN XY: 74392

African (AFR) AF: 0.128 AC: 5299 AN: 41502

American (AMR) AF: 0.0647 AC: 990 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5186

South Asian (SAS) AF: 0.0861 AC: 415 AN: 4820

European-Finnish (FIN) AF: 0.204 AC: 2164 AN: 10594

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

European-Non Finnish (NFE) AF: 0.146 AC: 9930 AN: 68004

Other (OTH) AF: 0.0903 AC: 191 AN: 2114

Alfa AF: 0.125 Hom.: 1958

Bravo AF: 0.113

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.79
PhyloP100		0.91
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: rs10199628; hg19: chr2-100735856;