rs3743591

Variant names:

• chr16-11965175-A-G
• rs3743591
• NM_001395854.1:c.-536-1149T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-11965175-A-G
• chr16-11965175-A-T

Variant summary

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

The NM_001395854.1(NPIPB2):​c.-536-1149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 904,702 control chromosomes in the GnomAD database, including 4,846 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 0.12 (1508 hom., cov: 33)
  • Exomes 𝑓: 0.071 (3338 hom.)
• Consequence: NPIPB2 NM_001395854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 10 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 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.-536-1149T>C		intron	N/A	NP_001382783.1
	NPIPB2	NM_001395855.1		c.-400-8938T>C		intron	N/A	NP_001382784.1
	NPIPB2	NM_001395852.1		c.-536-1149T>C		intron	N/A	NP_001382781.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB2	ENST00000673243.1		c.-536-1149T>C		intron	N/A	ENSP00000500799.1
	NPIPB2	ENST00000538896.5	TSL:5	c.-584+11393T>C		intron	N/A	ENSP00000442069.1
	NPIPB2	ENST00000532936.1	TSL:4	n.77-1149T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17717 AN: 152134 Hom.: 1503 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0871

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0711 AC: 53477 AN: 752450 Hom.: 3338 Cov.: 10 AF XY: 0.0678 AC XY: 26303 AN XY: 388208

African (AFR) AF: 0.217 AC: 4028 AN: 18596

American (AMR) AF: 0.289 AC: 7851 AN: 27160

Ashkenazi Jewish (ASJ) AF: 0.0993 AC: 1621 AN: 16324

East Asian (EAS) AF: 0.169 AC: 6075 AN: 35960

South Asian (SAS) AF: 0.0326 AC: 1814 AN: 55728

European-Finnish (FIN) AF: 0.0899 AC: 3519 AN: 39164

Middle Eastern (MID) AF: 0.0737 AC: 250 AN: 3390

European-Non Finnish (NFE) AF: 0.0488 AC: 25376 AN: 519998

Other (OTH) AF: 0.0815 AC: 2943 AN: 36130

GnomAD4 genome AF: 0.117 AC: 17744 AN: 152252 Hom.: 1508 Cov.: 33 AF XY: 0.118 AC XY: 8776 AN XY: 74446

African (AFR) AF: 0.210 AC: 8734 AN: 41530

American (AMR) AF: 0.197 AC: 3004 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3470

East Asian (EAS) AF: 0.155 AC: 802 AN: 5182

South Asian (SAS) AF: 0.0310 AC: 150 AN: 4832

European-Finnish (FIN) AF: 0.0871 AC: 925 AN: 10618

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0508 AC: 3457 AN: 68028

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.0745 Hom.: 2245

Bravo AF: 0.135

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.23
DANN	Benign	0.51
PhyloP100		-2.0
PromoterAI		-0.0070	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: rs3743591; hg19: chr16-12059032; COSMIC: COSV50000494; COSMIC: COSV50000494;