11-13492716-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000315.4(PTH):c.87-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,613,372 control chromosomes in the GnomAD database, including 85,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (6236 hom., cov: 32)
  • Exomes 𝑓: 0.32 (79367 hom.)
• Consequence: PTH NM_000315.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.298

Genes affected

PTH (HGNC:9606): (parathyroid hormone) This gene encodes a member of the parathyroid family of proteins. The encoded preproprotein is proteolytically processed to generate a protein that binds to the parathyroid hormone/parathyroid hormone-related peptide receptor and regulates blood calcium and phosphate levels. Excess production of the encoded protein, known as hyperparathyroidism, can result in hypercalcemia and kidney stones. On the other hand, defective processing of the encoded protein may lead to hypoparathyroidism, which can result in hypocalcemia and numbness. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-13492716-C-T is Benign according to our data. Variant chr11-13492716-C-T is described in ClinVar as [Benign]. Clinvar id is 1289830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTH	NM_000315.4	c.87-50G>A		intron_variant		ENST00000282091.6
PTH	NM_001316352.2	c.183-50G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTH	ENST00000282091.6	c.87-50G>A		intron_variant		1	NM_000315.4	P1
PTH	ENST00000529816.1	c.87-50G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39613 AN: 151932 Hom.: 6240 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.260

GnomAD3 exomes AF: 0.283 AC: 70884 AN: 250436 Hom.: 11350 AF XY: 0.286 AC XY: 38709 AN XY: 135336

Gnomad AFR exome AF: 0.0871

Gnomad AMR exome AF: 0.221

Gnomad ASJ exome AF: 0.304

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.354

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.321 AC: 469593 AN: 1461322 Hom.: 79367 Cov.: 42 AF XY: 0.319 AC XY: 231828 AN XY: 726924

Gnomad4 AFR exome AF: 0.0820

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.402

Gnomad4 NFE exome AF: 0.348

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.261 AC: 39612 AN: 152050 Hom.: 6236 Cov.: 32 AF XY: 0.261 AC XY: 19398 AN XY: 74316

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.257

Alfa AF: 0.311 Hom.: 8826

Bravo AF: 0.241

Asia WGS AF: 0.156 AC: 543 AN: 3478

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

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.6
Dann	Benign	0.60

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: rs6254; hg19: chr11-13514263; COSMIC: COSV56378553; COSMIC: COSV56378553;