dbSNP rs11739417: AFF4:c.2397-37T>C (chr5-132892441-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014423.4(AFF4):c.2397-37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,582,724 control chromosomes in the GnomAD database, including 30,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3535 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26983 hom. )

Consequence

AFF4
NM_014423.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.293

Variant links:

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]

AFF4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-132892441-A-G is Benign according to our data. Variant chr5-132892441-A-G is described in ClinVar as [Benign]. Clinvar id is 1248920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFF4	NM_014423.4 link	c.2397-37T>C		intron_variant	Intron 12 of 20	ENST00000265343.10	NP_055238.1	Q9UHB7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFF4	ENST00000265343.10 link	c.2397-37T>C		intron_variant	Intron 12 of 20	1	NM_014423.4	ENSP00000265343.5		Q9UHB7-1
AFF4	ENST00000378595.7 link	c.2397-37T>C		intron_variant	Intron 12 of 12	1		ENSP00000367858.3		Q9UHB7-2

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31378

AN:

151982

Hom.:

3527

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0848

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.223

GnomAD3 exomes

AF:

0.167

AC:

38238

AN:

228466

Hom.:

3573

AF XY:

0.164

AC XY:

20346

AN XY:

123886

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.0915

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.190

AC:

271303

AN:

1430624

Hom.:

26983

Cov.:

AF XY:

0.188

AC XY:

133082

AN XY:

708410

show subpopulations

Gnomad4 AFR exome

AF:

0.302

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.0927

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.207

AC:

31411

AN:

152100

Hom.:

3535

Cov.:

AF XY:

0.199

AC XY:

14833

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.286

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.190

Gnomad4 EAS

AF:

0.140

Gnomad4 SAS

AF:

0.0853

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.198

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.129

Hom.:

301

Bravo

AF:

0.217

Asia WGS

AF:

0.106

AC:

369

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

May 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.4

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over