17-16933111-G-A

Variant names:

• chr17-16933111-G-A
• rs3751987
• ENST00000261651.6:n.1626C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000261651.6(ENSG00000290698):​n.1626C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 691,942 control chromosomes in the GnomAD database, including 48,038 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 0.36 (10276 hom., cov: 32)
  • Exomes 𝑓: 0.37 (37762 hom.)
• Consequence: ENSG00000290698 ENST00000261651.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 9 publications found

Genes affected

ENSG00000290698 (HGNC:):

TNFRSF13B (HGNC:18153): (TNF receptor superfamily member 13B) The protein encoded by this gene is a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily. It interacts with calcium-modulator and cyclophilin ligand (CAML). The protein induces activation of the transcription factors NFAT, AP1, and NF-kappa-B and plays a crucial role in humoral immunity by interacting with a TNF ligand. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

TBC1D27P (HGNC:28104): (TBC1 domain family member 27, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.063).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000261651.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D27P	NR_147084.1		n.66C>T		non_coding_transcript_exon	Exon 1 of 13

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000290698	ENST00000261651.6	TSL:2	n.1626C>T		non_coding_transcript_exon	Exon 2 of 14
	TNFRSF13B	ENST00000584950.5	TSL:5	n.701C>T		non_coding_transcript_exon	Exon 5 of 10	ENSP00000463582.1
	TNFRSF13B	ENST00000579315.5	TSL:3	c.*40C>T		3_prime_UTR	Exon 4 of 4	ENSP00000464069.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55266 AN: 151870 Hom.: 10260 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.366

GnomAD2 exomes AF: 0.370 AC: 44245 AN: 119592 AF XY: 0.370

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.431

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.346

Gnomad OTH exome AF: 0.355

GnomAD4 exome AF: 0.369 AC: 199459 AN: 539952 Hom.: 37762 Cov.: 0 AF XY: 0.372 AC XY: 108861 AN XY: 292716

African (AFR) AF: 0.350 AC: 5330 AN: 15234

American (AMR) AF: 0.398 AC: 12790 AN: 32100

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 7429 AN: 19602

East Asian (EAS) AF: 0.480 AC: 15151 AN: 31590

South Asian (SAS) AF: 0.400 AC: 24282 AN: 60774

European-Finnish (FIN) AF: 0.317 AC: 10460 AN: 33024

Middle Eastern (MID) AF: 0.387 AC: 1561 AN: 4034

European-Non Finnish (NFE) AF: 0.355 AC: 111215 AN: 313488

Other (OTH) AF: 0.373 AC: 11241 AN: 30106

GnomAD4 genome AF: 0.364 AC: 55313 AN: 151990 Hom.: 10276 Cov.: 32 AF XY: 0.364 AC XY: 27067 AN XY: 74286

African (AFR) AF: 0.357 AC: 14805 AN: 41430

American (AMR) AF: 0.412 AC: 6290 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1365 AN: 3470

East Asian (EAS) AF: 0.462 AC: 2388 AN: 5170

South Asian (SAS) AF: 0.395 AC: 1899 AN: 4802

European-Finnish (FIN) AF: 0.311 AC: 3283 AN: 10568

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24086 AN: 67956

Other (OTH) AF: 0.364 AC: 769 AN: 2112

Alfa AF: 0.360 Hom.: 28306

Bravo AF: 0.370

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.9
DANN	Benign	0.92
PhyloP100		0.043
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3751987; hg19: chr17-16836425;