2-99647995-G-T

Position:

• chr2-99647995-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001386135.1(AFF3):​c.1184+1631C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 152,222 control chromosomes in the GnomAD database, including 106 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 0.034 (106 hom., cov: 33)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366

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=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0338 (5152/152222) while in subpopulation NFE AF= 0.0433 (2944/67998). AF 95% confidence interval is 0.042. There are 106 homozygotes in gnomad4. There are 2489 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5152 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFF3	NM_001386135.1	c.1184+1631C>A		intron_variant		ENST00000672756.2	NP_001373064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFF3	ENST00000672756.2	c.1184+1631C>A		intron_variant			NM_001386135.1	ENSP00000500419	A2

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5149 AN: 152104 Hom.: 106 Cov.: 33

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.0350

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.0390

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0433

Gnomad OTH AF: 0.0307

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

GnomAD4 genome AF: 0.0338 AC: 5152 AN: 152222 Hom.: 106 Cov.: 33 AF XY: 0.0334 AC XY: 2489 AN XY: 74416

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.0352

Gnomad4 SAS AF: 0.00893

Gnomad4 FIN AF: 0.0390

Gnomad4 NFE AF: 0.0433

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0132 Hom.: 6

Bravo AF: 0.0336

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs10514778; hg19: chr2-100264457;