NM_001192.3:c.477G>A

Variant names:

• chr16-11967769-G-A
• rs2017662
• NM_001192.3:c.477G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001192.3(TNFRSF17):​c.477G>A​(p.Thr159Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 1,614,082 control chromosomes in the GnomAD database, including 7,062 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 (1489 hom., cov: 32)
  • Exomes 𝑓: 0.065 (5573 hom.)
• Consequence: TNFRSF17 NM_001192.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• Publications: 16 publications found

Genes affected

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]

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.559 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001192.3. 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
	TNFRSF17	NM_001192.3	MANE Select	c.477G>A	p.Thr159Thr	synonymous	Exon 3 of 3	NP_001183.2
	NPIPB2	NM_001395854.1		c.-536-3743C>T		intron	N/A	NP_001382783.1	A0A5F9ZI19
	NPIPB2	NM_001395855.1		c.-401+8799C>T		intron	N/A	NP_001382784.1	A0A5F9ZI19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF17	ENST00000053243.6	TSL:1 MANE Select	c.477G>A	p.Thr159Thr	synonymous	Exon 3 of 3	ENSP00000053243.1	Q02223-1
	TNFRSF17	ENST00000396495.3	TSL:1	c.330G>A	p.Thr110Thr	synonymous	Exon 2 of 2	ENSP00000379753.3	Q02223-2
	NPIPB2	ENST00000673243.1		c.-536-3743C>T		intron	N/A	ENSP00000500799.1	A0A5F9ZI19

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17620 AN: 152092 Hom.: 1484 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0305

Gnomad FIN AF: 0.0872

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0507

Gnomad OTH AF: 0.110

GnomAD2 exomes AF: 0.110 AC: 27756 AN: 251416 AF XY: 0.0969

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.320

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.150

Gnomad FIN exome AF: 0.0903

Gnomad NFE exome AF: 0.0526

Gnomad OTH exome AF: 0.0875

GnomAD4 exome AF: 0.0651 AC: 95216 AN: 1461872 Hom.: 5573 Cov.: 32 AF XY: 0.0630 AC XY: 45783 AN XY: 727240

African (AFR) AF: 0.218 AC: 7300 AN: 33480

American (AMR) AF: 0.303 AC: 13566 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2691 AN: 26136

East Asian (EAS) AF: 0.167 AC: 6641 AN: 39698

South Asian (SAS) AF: 0.0326 AC: 2809 AN: 86258

European-Finnish (FIN) AF: 0.0918 AC: 4904 AN: 53416

Middle Eastern (MID) AF: 0.0754 AC: 435 AN: 5768

European-Non Finnish (NFE) AF: 0.0470 AC: 52282 AN: 1112004

Other (OTH) AF: 0.0760 AC: 4588 AN: 60396

GnomAD4 genome AF: 0.116 AC: 17648 AN: 152210 Hom.: 1489 Cov.: 32 AF XY: 0.117 AC XY: 8734 AN XY: 74420

African (AFR) AF: 0.210 AC: 8709 AN: 41532

American (AMR) AF: 0.193 AC: 2951 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3472

East Asian (EAS) AF: 0.155 AC: 801 AN: 5170

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4822

European-Finnish (FIN) AF: 0.0872 AC: 925 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0507 AC: 3446 AN: 68010

Other (OTH) AF: 0.109 AC: 230 AN: 2110

Alfa AF: 0.0817 Hom.: 1324

Bravo AF: 0.133

Asia WGS AF: 0.113 AC: 395 AN: 3478

EpiCase AF: 0.0504

EpiControl AF: 0.0519

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.58
DANN	Benign	0.91
PhyloP100		-0.56
Mutation Taster		=100/0	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: rs2017662; hg19: chr16-12061626; COSMIC: COSV50000597; COSMIC: COSV50000597;