16-11965181-C-T

Variant names:

• chr16-11965181-C-T
• rs11570139
• NM_001395854.1:c.-536-1155G>A

Variant summary

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

The NM_001395854.1(NPIPB2):​c.-536-1155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,026,146 control chromosomes in the GnomAD database, including 40,467 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 0.21 (4143 hom., cov: 33)
  • Exomes 𝑓: 0.27 (36324 hom.)
• Consequence: NPIPB2 NM_001395854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 12 publications found

Genes affected

NPIPB2 (HGNC:37451): (nuclear pore complex interacting protein family member B2) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TNFRSF17 (HGNC:11913): (TNF receptor superfamily member 17) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature B lymphocytes, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395854.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB2	NM_001395854.1		c.-536-1155G>A		intron	N/A	NP_001382783.1	A0A5F9ZI19
	NPIPB2	NM_001395855.1		c.-400-8944G>A		intron	N/A	NP_001382784.1	A0A5F9ZI19
	NPIPB2	NM_001395852.1		c.-536-1155G>A		intron	N/A	NP_001382781.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB2	ENST00000673243.1		c.-536-1155G>A		intron	N/A	ENSP00000500799.1	A0A5F9ZI19
	NPIPB2	ENST00000538896.5	TSL:5	c.-584+11387G>A		intron	N/A	ENSP00000442069.1	F5H898
	NPIPB2	ENST00000532936.1	TSL:4	n.77-1155G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31623 AN: 152088 Hom.: 4145 Cov.: 33

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.273 AC: 238711 AN: 873940 Hom.: 36324 Cov.: 12 AF XY: 0.269 AC XY: 119917 AN XY: 445296

African (AFR) AF: 0.0657 AC: 1388 AN: 21130

American (AMR) AF: 0.152 AC: 4427 AN: 29212

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 4682 AN: 17482

East Asian (EAS) AF: 0.0144 AC: 527 AN: 36592

South Asian (SAS) AF: 0.135 AC: 7967 AN: 59092

European-Finnish (FIN) AF: 0.222 AC: 8881 AN: 40000

Middle Eastern (MID) AF: 0.225 AC: 844 AN: 3748

European-Non Finnish (NFE) AF: 0.319 AC: 199675 AN: 626620

Other (OTH) AF: 0.258 AC: 10320 AN: 40064

GnomAD4 genome AF: 0.208 AC: 31622 AN: 152206 Hom.: 4143 Cov.: 33 AF XY: 0.198 AC XY: 14770 AN XY: 74418

African (AFR) AF: 0.0716 AC: 2974 AN: 41554

American (AMR) AF: 0.196 AC: 2990 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 895 AN: 3472

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5182

South Asian (SAS) AF: 0.127 AC: 611 AN: 4816

European-Finnish (FIN) AF: 0.214 AC: 2265 AN: 10604

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 21020 AN: 67990

Other (OTH) AF: 0.246 AC: 520 AN: 2110

Alfa AF: 0.259 Hom.: 9020

Bravo AF: 0.202

Asia WGS AF: 0.0730 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.9
DANN	Benign	0.80
PhyloP100		-0.077
PromoterAI		0.021	Neutral
Mutation Taster		=300/0	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: rs11570139; hg19: chr16-12059038;