rs1952994

chr13-32528739-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014887.3(N4BP2L2):c.1260-1207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 152,152 control chromosomes in the GnomAD database, including 574 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 0.078 (574 hom., cov: 32)
• Consequence: N4BP2L2 NM_014887.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399

Genes affected

N4BP2L2 (HGNC:26916): (NEDD4 binding protein 2 like 2) Enables enzyme binding activity. Involved in negative regulation of hematopoietic stem cell differentiation and positive regulation of hematopoietic stem cell proliferation. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
N4BP2L2	NM_014887.3	c.1260-1207T>C		intron_variant		ENST00000267068.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
N4BP2L2	ENST00000267068.6	c.1260-1207T>C		intron_variant		1	NM_014887.3	P2

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11917 AN: 152034 Hom.: 569 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0809

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.0738

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

GnomAD4 genome AF: 0.0785 AC: 11938 AN: 152152 Hom.: 574 Cov.: 32 AF XY: 0.0775 AC XY: 5766 AN XY: 74398

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0814

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.0680

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.0628

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.0644 Hom.: 738

Bravo AF: 0.0837

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.6
Dann	Benign	0.75

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: rs1952994; hg19: chr13-33102876;