rs2525485

Variant names:

• chr5-132883095-C-A
• rs2525485
• NM_014423.4:c.3364+245G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-132883095-C-A
• chr5-132883095-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

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

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014423.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFF4	NM_014423.4	MANE Select	c.3364+245G>T		intron	N/A	NP_055238.1	Q9UHB7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFF4	ENST00000265343.10	TSL:1 MANE Select	c.3364+245G>T		intron	N/A	ENSP00000265343.5	Q9UHB7-1
	AFF4	ENST00000944867.1		c.3394+245G>T		intron	N/A	ENSP00000614926.1
	AFF4	ENST00000909435.1		c.2446+245G>T		intron	N/A	ENSP00000579494.1

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

African (AFR) AF: 0.247 AC: 10227 AN: 41396

American (AMR) AF: 0.470 AC: 7173 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1906 AN: 3468

East Asian (EAS) AF: 0.285 AC: 1471 AN: 5154

South Asian (SAS) AF: 0.588 AC: 2828 AN: 4812

European-Finnish (FIN) AF: 0.476 AC: 5003 AN: 10508

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36227 AN: 67932

Other (OTH) AF: 0.437 AC: 918 AN: 2102

Alfa AF: 0.366 Hom.: 1491

Bravo AF: 0.420

Asia WGS AF: 0.436 AC: 1518 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.33
PhyloP100		-0.058
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2525485; hg19: chr5-132218787;