NM_001386135.1:c.874-6668G>A

Variant names:

• chr2-99844192-C-T
• rs7583877
• NM_001386135.1:c.874-6668G>A

Variant summary

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

The NM_001386135.1(AFF3):​c.874-6668G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,052 control chromosomes in the GnomAD database, including 29,995 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 0.62 (29995 hom., cov: 33)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 32 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

ENSG00000299017 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFF3	NM_001386135.1	c.874-6668G>A		intron_variant	Intron 7 of 24	ENST00000672756.2	NP_001373064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFF3	ENST00000672756.2	c.874-6668G>A		intron_variant	Intron 7 of 24		NM_001386135.1	ENSP00000500419.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93895 AN: 151934 Hom.: 30003 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.618 AC: 93900 AN: 152052 Hom.: 29995 Cov.: 33 AF XY: 0.624 AC XY: 46350 AN XY: 74334

African (AFR) AF: 0.453 AC: 18759 AN: 41444

American (AMR) AF: 0.578 AC: 8831 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2427 AN: 3468

East Asian (EAS) AF: 0.642 AC: 3318 AN: 5168

South Asian (SAS) AF: 0.754 AC: 3639 AN: 4826

European-Finnish (FIN) AF: 0.767 AC: 8107 AN: 10574

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46643 AN: 67984

Other (OTH) AF: 0.626 AC: 1320 AN: 2110

Alfa AF: 0.642 Hom.: 51249

Bravo AF: 0.590

Asia WGS AF: 0.635 AC: 2211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.085
DANN	Benign	0.43
PhyloP100		-1.8
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: rs7583877; hg19: chr2-100460654;