5-132883258-A-G

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+82T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00763 in 1,272,346 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (84 hom., cov: 33)
  • Exomes 𝑓: 0.0058 (72 hom.)
• Consequence: AFF4 NM_014423.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.316

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=-0.92).
• BP6: Variant 5-132883258-A-G is Benign according to our data. Variant chr5-132883258-A-G is described in ClinVar as [Benign]. Clinvar id is 1267749.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFF4	NM_014423.4	c.3364+82T>C		intron_variant		ENST00000265343.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFF4	ENST00000265343.10	c.3364+82T>C		intron_variant		1	NM_014423.4	P1

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3197 AN: 152236 Hom.: 83 Cov.: 33

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00473

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.00581 AC: 6503 AN: 1119992 Hom.: 72 AF XY: 0.00565 AC XY: 3191 AN XY: 565072

Gnomad4 AFR exome AF: 0.0527

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.0207

Gnomad4 EAS exome AF: 0.000107

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.000197

Gnomad4 NFE exome AF: 0.00422

Gnomad4 OTH exome AF: 0.0109

GnomAD4 genome AF: 0.0210 AC: 3204 AN: 152354 Hom.: 84 Cov.: 33 AF XY: 0.0204 AC XY: 1523 AN XY: 74510

Gnomad4 AFR AF: 0.0578

Gnomad4 AMR AF: 0.0170

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00473

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0142 Hom.: 2

Bravo AF: 0.0243

Asia WGS AF: 0.0140 AC: 47 AN: 3478

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 23, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.4
Dann	Benign	0.41

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: rs73788220; hg19: chr5-132218950;