rs207650

Positions:

• chr13-32487100-A-G

Variant summary

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

The NM_001320836.3(N4BP2L2):​c.1697+30757T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,010 control chromosomes in the GnomAD database, including 11,372 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 0.38 (11372 hom., cov: 32)
• Consequence: N4BP2L2 NM_001320836.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
N4BP2L2	NM_001278432.2	c.365+30757T>C		intron_variant			NP_001265361.1
N4BP2L2	NM_001320836.3	c.1697+30757T>C		intron_variant			NP_001307765.1
N4BP2L2	NM_001387001.1	c.1697+30757T>C		intron_variant			NP_001373930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
N4BP2L2	ENST00000357505.10	c.365+30757T>C		intron_variant		2		ENSP00000350104
N4BP2L2	ENST00000399396.7	c.410+30757T>C		intron_variant		5		ENSP00000382328
N4BP2L2	ENST00000446957.6	c.1697+30757T>C		intron_variant		5		ENSP00000394239	A2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58404 AN: 151890 Hom.: 11363 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.385 AC: 58451 AN: 152010 Hom.: 11372 Cov.: 32 AF XY: 0.382 AC XY: 28410 AN XY: 74302

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.366

Alfa AF: 0.385 Hom.: 1411

Bravo AF: 0.379

Asia WGS AF: 0.391 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs207650; hg19: chr13-33061237;