rs17437101

Variant names:

• chr2-99998779-G-A
• rs17437101
• NM_001386135.1:c.873+7853C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-99998779-G-A
• chr2-99998779-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386135.1(AFF3):​c.873+7853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,150 control chromosomes in the GnomAD database, including 1,211 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1211 hom., cov: 32)
• Consequence: AFF3 NM_001386135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 4 publications found

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]

AFF3 Gene-Disease associations (from GenCC):

• KINSSHIP syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• intellectual disability

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFF3	NM_001386135.1	c.873+7853C>T		intron_variant	Intron 7 of 24	ENST00000672756.2	NP_001373064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFF3	ENST00000672756.2	c.873+7853C>T		intron_variant	Intron 7 of 24		NM_001386135.1	ENSP00000500419.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16376 AN: 152032 Hom.: 1211 Cov.: 32

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.0814

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

GnomAD4 genome AF: 0.108 AC: 16373 AN: 152150 Hom.: 1211 Cov.: 32 AF XY: 0.109 AC XY: 8136 AN XY: 74380

African (AFR) AF: 0.0473 AC: 1963 AN: 41518

American (AMR) AF: 0.0659 AC: 1008 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0697 AC: 336 AN: 4822

European-Finnish (FIN) AF: 0.228 AC: 2414 AN: 10568

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10313 AN: 67992

Other (OTH) AF: 0.0806 AC: 170 AN: 2110

Alfa AF: 0.123 Hom.: 1686

Bravo AF: 0.0902

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.024
DANN	Benign	0.67
PhyloP100		-2.3
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: rs17437101; hg19: chr2-100615241;