rs11862958

chr16-11961334-C-T

Variant summary

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

The NM_001395854.1(NPIPB2):c.-401+2557G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,068 control chromosomes in the GnomAD database, including 6,904 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 0.27 (6904 hom., cov: 31)
• Consequence: NPIPB2 NM_001395854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

Genes affected

NPIPB2 (HGNC:37451): (nuclear pore complex interacting protein family member B2) Located in nucleoplasm. [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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPB2	NM_001355514.1	c.-401+2557G>A		intron_variant
NPIPB2	NM_001395852.1	c.-401+2557G>A		intron_variant
NPIPB2	NM_001395853.1	c.-400-5097G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPIPB2	ENST00000538896.5	c.-584+15234G>A		intron_variant		5
NPIPB2	ENST00000673243.1	c.-401+2557G>A		intron_variant
NPIPB2	ENST00000532936.1	n.212+2557G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41422 AN: 151950 Hom.: 6904 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.272 AC: 41427 AN: 152068 Hom.: 6904 Cov.: 31 AF XY: 0.263 AC XY: 19524 AN XY: 74336

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.324

Alfa AF: 0.350 Hom.: 6365

Bravo AF: 0.269

Asia WGS AF: 0.0930 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.012
Dann	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11862958; hg19: chr16-12055191;