16-28638441-T-C

Position:

• chr16-28638441-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001310136.2(NPIPB8):​c.81T>C​(p.His27His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,572,940 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (14 hom., cov: 30)
  • Exomes 𝑓: 0.0013 (24 hom.)
• Consequence: NPIPB8 NM_001310136.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.52

Genes affected

NPIPB8 (HGNC:37490): (nuclear pore complex interacting protein family member B8) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-28638441-T-C is Benign according to our data. Variant chr16-28638441-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2646353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.52 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPIPB8	NM_001310136.2	c.81T>C	p.His27His	synonymous_variant	2/8	ENST00000683297.1	NP_001297065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPIPB8	ENST00000683297.1	c.81T>C	p.His27His	synonymous_variant	2/8		NM_001310136.2	ENSP00000507410.1
NPIPB8	ENST00000529716.5	c.81T>C	p.His27His	synonymous_variant	1/7	5		ENSP00000434399.1

Frequencies

GnomAD3 genomes AF: 0.00275 AC: 413 AN: 149924 Hom.: 14 Cov.: 30

Gnomad AFR AF: 0.00595

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00212

Gnomad ASJ AF: 0.00751

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.000571

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.00388

GnomAD3 exomes AF: 0.00217 AC: 438 AN: 201560 Hom.: 9 AF XY: 0.00207 AC XY: 227 AN XY: 109428

Gnomad AFR exome AF: 0.00641

Gnomad AMR exome AF: 0.00362

Gnomad ASJ exome AF: 0.00880

Gnomad EAS exome AF: 0.000242

Gnomad SAS exome AF: 0.000654

Gnomad FIN exome AF: 0.000788

Gnomad NFE exome AF: 0.00128

Gnomad OTH exome AF: 0.00493

GnomAD4 exome AF: 0.00127 AC: 1809 AN: 1422902 Hom.: 24 Cov.: 41 AF XY: 0.00131 AC XY: 927 AN XY: 706040

Gnomad4 AFR exome AF: 0.00674

Gnomad4 AMR exome AF: 0.00284

Gnomad4 ASJ exome AF: 0.00843

Gnomad4 EAS exome AF: 0.000153

Gnomad4 SAS exome AF: 0.000753

Gnomad4 FIN exome AF: 0.00102

Gnomad4 NFE exome AF: 0.000837

Gnomad4 OTH exome AF: 0.00270

GnomAD4 genome AF: 0.00277 AC: 415 AN: 150038 Hom.: 14 Cov.: 30 AF XY: 0.00269 AC XY: 197 AN XY: 73334

Gnomad4 AFR AF: 0.00598

Gnomad4 AMR AF: 0.00211

Gnomad4 ASJ AF: 0.00751

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000418

Gnomad4 FIN AF: 0.000571

Gnomad4 NFE AF: 0.00146

Gnomad4 OTH AF: 0.00384

Alfa AF: 0.00159 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

NPIPB8: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.84

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: rs536341295; hg19: chr16-28649762; COSMIC: COSV73198464;