rs1437377

Positions:

• chr2-100128462-T-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+762A>C 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 152,108 control chromosomes in the GnomAD database, including 4,583 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 (4583 hom., cov: 32)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFF3	NM_001386135.1	c.-145+762A>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+762A>C		intron_variant			NM_001386135.1	ENSP00000500419	A2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31329 AN: 151990 Hom.: 4570 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0767

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.206 AC: 31384 AN: 152108 Hom.: 4583 Cov.: 32 AF XY: 0.200 AC XY: 14848 AN XY: 74350

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.0769

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.192

Alfa AF: 0.155 Hom.: 1047

Bravo AF: 0.217

Asia WGS AF: 0.147 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1437377; hg19: chr2-100744924; COSMIC: COSV57847490;