11-13492716-C-T

Variant names:

• chr11-13492716-C-T
• rs6254
• NM_000315.4:c.87-50G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• 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

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
PTH	NM_000315.4	c.87-50G>A		intron_variant	Intron 2 of 2	ENST00000282091.6	NP_000306.1
PTH	NM_001316352.2	c.183-50G>A		intron_variant	Intron 2 of 2		NP_001303281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTH	ENST00000282091.6	c.87-50G>A		intron_variant	Intron 2 of 2	1	NM_000315.4	ENSP00000282091.1
PTH	ENST00000529816.1	c.87-50G>A		intron_variant	Intron 2 of 2	5		ENSP00000433208.1

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

GnomAD2 exomes AF: 0.283 AC: 70884 AN: 250436 AF XY: 0.286

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 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 AC: 2746 AN: 33474

Gnomad4 AMR exome AF: 0.224 AC: 9990 AN: 44594

Gnomad4 ASJ exome AF: 0.302 AC: 7894 AN: 26128

Gnomad4 EAS exome AF: 0.104 AC: 4139 AN: 39694

Gnomad4 SAS exome AF: 0.195 AC: 16777 AN: 86240

Gnomad4 FIN exome AF: 0.402 AC: 21461 AN: 53364

Gnomad4 NFE exome AF: 0.348 AC: 387251 AN: 1111694

Gnomad4 Remaining exome AF: 0.294 AC: 17767 AN: 60366

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 AC: 0.0928692 AN: 0.0928692

Gnomad4 AMR AF: 0.258 AC: 0.258453 AN: 0.258453

Gnomad4 ASJ AF: 0.299 AC: 0.299135 AN: 0.299135

Gnomad4 EAS AF: 0.117 AC: 0.11668 AN: 0.11668

Gnomad4 SAS AF: 0.194 AC: 0.19411 AN: 0.19411

Gnomad4 FIN AF: 0.421 AC: 0.421332 AN: 0.421332

Gnomad4 NFE AF: 0.351 AC: 0.351243 AN: 0.351243

Gnomad4 OTH AF: 0.257 AC: 0.257116 AN: 0.257116

Alfa AF: 0.304 Hom.: 22516

Bravo AF: 0.241

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.60
Mutation Taster		=100/0	polymorphism (auto)

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;