rs373496

Variant names:

• chr16-11966306-A-G
• rs373496
• NM_001192.3:c.242A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-11966306-A-G
• chr16-11966306-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001192.3(TNFRSF17):​c.242A>G​(p.Asn81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,613,932 control chromosomes in the GnomAD database, including 780,504 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.96 (70790 hom., cov: 32)
  • Exomes 𝑓: 0.99 (709714 hom.)
• Consequence: TNFRSF17 NM_001192.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0640447E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF17	NM_001192.3	c.242A>G	p.Asn81Ser	missense_variant	Exon 2 of 3	ENST00000053243.6	NP_001183.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF17	ENST00000053243.6	c.242A>G	p.Asn81Ser	missense_variant	Exon 2 of 3	1	NM_001192.3	ENSP00000053243.1

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146602 AN: 152136 Hom.: 70755 Cov.: 32

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 0.987

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.979

GnomAD3 exomes AF: 0.982 AC: 246811 AN: 251354 Hom.: 121252 AF XY: 0.983 AC XY: 133510 AN XY: 135848

Gnomad AFR exome AF: 0.901

Gnomad AMR exome AF: 0.992

Gnomad ASJ exome AF: 0.988

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.972

Gnomad FIN exome AF: 0.993

Gnomad NFE exome AF: 0.988

Gnomad OTH exome AF: 0.985

GnomAD4 exome AF: 0.985 AC: 1440227 AN: 1461678 Hom.: 709714 Cov.: 44 AF XY: 0.985 AC XY: 716232 AN XY: 727122

Gnomad4 AFR exome AF: 0.900

Gnomad4 AMR exome AF: 0.990

Gnomad4 ASJ exome AF: 0.989

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.973

Gnomad4 FIN exome AF: 0.990

Gnomad4 NFE exome AF: 0.988

Gnomad4 OTH exome AF: 0.983

GnomAD4 genome AF: 0.963 AC: 146695 AN: 152254 Hom.: 70790 Cov.: 32 AF XY: 0.964 AC XY: 71784 AN XY: 74446

Gnomad4 AFR AF: 0.901

Gnomad4 AMR AF: 0.980

Gnomad4 ASJ AF: 0.987

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.975

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.987

Gnomad4 OTH AF: 0.978

Alfa AF: 0.984 Hom.: 152725

Bravo AF: 0.961

TwinsUK AF: 0.988 AC: 3665

ALSPAC AF: 0.991 AC: 3819

ESP6500AA AF: 0.899 AC: 3951

ESP6500EA AF: 0.988 AC: 8499

ExAC AF: 0.979 AC: 118881

Asia WGS AF: 0.977 AC: 3399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.097
DANN	Benign	0.48
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.0040
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.023
MPC		0.0073
ClinPred		0.0083	T
GERP RS		-3.1
Varity_R		0.037
gMVP		0.093

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs373496; hg19: chr16-12060163;