2-100119105-A-G

Variant names:

• chr2-100119105-A-G
• rs6743817
• NM_001386135.1:c.-145+10119T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386135.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFF3	NM_001386135.1	MANE Select	c.-145+10119T>C		intron	N/A	NP_001373064.1
	AFF3	NM_002285.3		c.-144-13522T>C		intron	N/A	NP_002276.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFF3	ENST00000672756.2	MANE Select	c.-145+10119T>C		intron	N/A	ENSP00000500419.1
	AFF3	ENST00000317233.8	TSL:5	c.-144-13522T>C		intron	N/A	ENSP00000317421.4
	AFF3	ENST00000672204.1		c.-144-13522T>C		intron	N/A	ENSP00000500616.1

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

African (AFR) AF: 0.251 AC: 10434 AN: 41500

American (AMR) AF: 0.0793 AC: 1214 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3466

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5180

South Asian (SAS) AF: 0.0862 AC: 415 AN: 4814

European-Finnish (FIN) AF: 0.205 AC: 2164 AN: 10580

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9954 AN: 68006

Other (OTH) AF: 0.116 AC: 245 AN: 2114

Alfa AF: 0.138 Hom.: 3295

Bravo AF: 0.154

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.59
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6743817; hg19: chr2-100735567;