NM_001386135.1:c.1184+18332C>T

Variant names:

• chr2-99631294-G-A
• rs12471490
• NM_001386135.1:c.1184+18332C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386135.1(AFF3):​c.1184+18332C>T 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 152,130 control chromosomes in the GnomAD database, including 2,487 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 (2487 hom., cov: 32)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFF3	NM_001386135.1	c.1184+18332C>T		intron_variant	Intron 13 of 24	ENST00000672756.2	NP_001373064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFF3	ENST00000672756.2	c.1184+18332C>T		intron_variant	Intron 13 of 24		NM_001386135.1	ENSP00000500419.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24631 AN: 152012 Hom.: 2489 Cov.: 32

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.162 AC: 24626 AN: 152130 Hom.: 2487 Cov.: 32 AF XY: 0.163 AC XY: 12147 AN XY: 74364

African (AFR) AF: 0.0437 AC: 1813 AN: 41506

American (AMR) AF: 0.148 AC: 2255 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 903 AN: 3470

East Asian (EAS) AF: 0.107 AC: 554 AN: 5180

South Asian (SAS) AF: 0.289 AC: 1387 AN: 4806

European-Finnish (FIN) AF: 0.190 AC: 2007 AN: 10590

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14944 AN: 67986

Other (OTH) AF: 0.180 AC: 379 AN: 2104

Alfa AF: 0.183 Hom.: 382

Bravo AF: 0.149

Asia WGS AF: 0.163 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.3
DANN	Benign	0.77
PhyloP100		0.35
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: rs12471490; hg19: chr2-100247756;