16-11967820-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001192.3(TNFRSF17):c.528G>C(p.Glu176Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000922 in 1,613,996 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0050 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (8 hom.)
• Consequence: TNFRSF17 NM_001192.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.60

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003256172).
• BP6: Variant 16-11967820-G-C is Benign according to our data. Variant chr16-11967820-G-C is described in ClinVar as [Benign]. Clinvar id is 779009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00499 (760/152316) while in subpopulation AFR AF= 0.0175 (729/41560). AF 95% confidence interval is 0.0165. There are 14 homozygotes in gnomad4. There are 384 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF17	NM_001192.3	c.528G>C	p.Glu176Asp	missense_variant	3/3	ENST00000053243.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF17	ENST00000053243.6	c.528G>C	p.Glu176Asp	missense_variant	3/3	1	NM_001192.3	P1

Frequencies

GnomAD3 genomes AF: 0.00489 AC: 745 AN: 152198 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00136 AC: 342 AN: 251108 Hom.: 3 AF XY: 0.00107 AC XY: 145 AN XY: 135728

Gnomad AFR exome AF: 0.0187

Gnomad AMR exome AF: 0.000929

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000817

GnomAD4 exome AF: 0.000498 AC: 728 AN: 1461680 Hom.: 8 Cov.: 31 AF XY: 0.000458 AC XY: 333 AN XY: 727120

Gnomad4 AFR exome AF: 0.0175

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.00499 AC: 760 AN: 152316 Hom.: 14 Cov.: 32 AF XY: 0.00516 AC XY: 384 AN XY: 74474

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000771 Hom.: 1

Bravo AF: 0.00576

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0159 AC: 70

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00169 AC: 205

Asia WGS AF: 0.00375 AC: 14 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	15
Dann	Benign	0.94
DEOGEN2	Benign	0.29	T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.54	T;T
MetaRNN	Benign	0.0033	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.11
Sift	Benign	0.42	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.12	B;.
Vest4		0.075
MutPred		0.10		Loss of helix (P = 0.079);.;
MVP		0.29
MPC		0.0082
ClinPred		0.021	T
GERP RS		5.2
Varity_R		0.068
gMVP		0.12

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: rs34546237; hg19: chr16-12061677;