Menu
GeneBe

2-99554396-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001386135.1(AFF3):c.3474G>A(p.Ala1158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,614,150 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00077 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

AFF3
NM_001386135.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.00
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-99554396-C-T is Benign according to our data. Variant chr2-99554396-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 118 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AFF3NM_001386135.1 linkuse as main transcriptc.3474G>A p.Ala1158= synonymous_variant 24/25 ENST00000672756.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AFF3ENST00000672756.2 linkuse as main transcriptc.3474G>A p.Ala1158= synonymous_variant 24/25 NM_001386135.1 A2P51826-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000776
AC:
118
AN:
152154
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.000289
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00187
Gnomad FIN
AF:
0.000847
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00113
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.00100
AC:
252
AN:
251466
Hom.:
0
AF XY:
0.00112
AC XY:
152
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.000492
Gnomad AMR exome
AF:
0.000781
Gnomad ASJ exome
AF:
0.000298
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00167
Gnomad FIN exome
AF:
0.000601
Gnomad NFE exome
AF:
0.00127
Gnomad OTH exome
AF:
0.000815
GnomAD4 exome
AF:
0.00110
AC:
1608
AN:
1461878
Hom.:
2
Cov.:
32
AF XY:
0.00118
AC XY:
859
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.000827
Gnomad4 ASJ exome
AF:
0.000230
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00147
Gnomad4 FIN exome
AF:
0.000562
Gnomad4 NFE exome
AF:
0.00119
Gnomad4 OTH exome
AF:
0.00109
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000775
AC:
118
AN:
152272
Hom.:
1
Cov.:
32
AF XY:
0.000618
AC XY:
46
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.000289
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.000847
Gnomad4 NFE
AF:
0.00113
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.00111
Hom.:
0
Bravo
AF:
0.000805
EpiCase
AF:
0.00202
EpiControl
AF:
0.00267

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2022AFF3: BP4, BP7 -
AFF3-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesSep 05, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
8.4
Dann
Benign
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs141110020; hg19: chr2-100170858; API