2-100119105-A-G

Position:

• chr2-100119105-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386135.1(AFF3):​c.-145+10119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,166 control chromosomes in the GnomAD database, including 2,389 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 0.16 (2389 hom., cov: 33)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFF3	NM_001386135.1	c.-145+10119T>C		intron_variant		ENST00000672756.2	NP_001373064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFF3	ENST00000672756.2	c.-145+10119T>C		intron_variant			NM_001386135.1	ENSP00000500419	A2

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24589 AN: 152048 Hom.: 2386 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.162 AC: 24610 AN: 152166 Hom.: 2389 Cov.: 33 AF XY: 0.160 AC XY: 11888 AN XY: 74386

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.0793

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0862

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.116

Alfa AF: 0.127 Hom.: 1848

Bravo AF: 0.154

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6743817; hg19: chr2-100735567;