5-132883095-C-A

Position:

• chr5-132883095-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014423.4(AFF4):​c.3364+245G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,838 control chromosomes in the GnomAD database, including 15,775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (15775 hom., cov: 31)
• Consequence: AFF4 NM_014423.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0580

Genes affected

AFF4 (HGNC:17869): (ALF transcription elongation factor 4) The protein encoded by this gene belongs to the AF4 family of transcription factors involved in leukemia. It is a component of the positive transcription elongation factor b (P-TEFb) complex. A chromosomal translocation involving this gene and MLL gene on chromosome 11 is found in infant acute lymphoblastic leukemia with ins(5;11)(q31;q31q23). [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-132883095-C-A is Benign according to our data. Variant chr5-132883095-C-A is described in ClinVar as [Benign]. Clinvar id is 1286410.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFF4	NM_014423.4	c.3364+245G>T		intron_variant		ENST00000265343.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFF4	ENST00000265343.10	c.3364+245G>T		intron_variant		1	NM_014423.4	P1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66382 AN: 151720 Hom.: 15780 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.437 AC: 66403 AN: 151838 Hom.: 15775 Cov.: 31 AF XY: 0.438 AC XY: 32470 AN XY: 74192

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.437

Alfa AF: 0.370 Hom.: 1456

Bravo AF: 0.420

Asia WGS AF: 0.436 AC: 1518 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs2525485; hg19: chr5-132218787;