rs3751987

Positions:

• chr17-16933111-G-A
• chr17-16933111-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NR_147084.1(TBC1D27P):​n.66C>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. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.36 (10276 hom., cov: 32)
  • Exomes 𝑓: 0.37 (37762 hom.)
• Consequence: TBC1D27P NR_147084.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

Genes affected

(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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-16933111-G-A is Benign according to our data. Variant chr17-16933111-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D27P	NR_147084.1	n.66C>T		non_coding_transcript_exon_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000261651.6	n.1626C>T		non_coding_transcript_exon_variant	2/14	2
TNFRSF13B	ENST00000579315.5	c.*40C>T		3_prime_UTR_variant	4/4	3		A2
TNFRSF13B	ENST00000584950.5	c.701C>T	p.Thr234Met	missense_variant, NMD_transcript_variant	5/10	5
TNFRSF13B	ENST00000582931.5	n.350-174C>T		intron_variant, non_coding_transcript_variant		4

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

GnomAD3 exomes AF: 0.370 AC: 44245 AN: 119592 Hom.: 8362 AF XY: 0.370 AC XY: 24381 AN XY: 65864

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 SAS exome AF: 0.392

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

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.480

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.373

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

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.364

Alfa AF: 0.362 Hom.: 10129

Bravo AF: 0.370

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.9
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3751987; hg19: chr17-16836425;