3-46901538-T-C

Position:

• chr3-46901538-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000316.3(PTH1R):​c.1116+58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,542,288 control chromosomes in the GnomAD database, including 256,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19992 hom., cov: 32)
  • Exomes 𝑓: 0.58 (236196 hom.)
• Consequence: PTH1R NM_000316.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.841

Genes affected

PTH1R (HGNC:9608): (parathyroid hormone 1 receptor) The protein encoded by this gene is a member of the G-protein coupled receptor family 2. This protein is a receptor for parathyroid hormone (PTH) and for parathyroid hormone-like hormone (PTHLH). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system. Defects in this receptor are known to be the cause of Jansen's metaphyseal chondrodysplasia (JMC), chondrodysplasia Blomstrand type (BOCD), as well as enchodromatosis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 3-46901538-T-C is Benign according to our data. Variant chr3-46901538-T-C is described in ClinVar as [Benign]. Clinvar id is 1231054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTH1R	NM_000316.3	c.1116+58T>C		intron_variant		ENST00000449590.6	NP_000307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTH1R	ENST00000449590.6	c.1116+58T>C		intron_variant		1	NM_000316.3	ENSP00000402723	P1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74763 AN: 151884 Hom.: 19971 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.580 AC: 805724 AN: 1390284 Hom.: 236196 Cov.: 30 AF XY: 0.579 AC XY: 397135 AN XY: 686268

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.505

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.599

Gnomad4 NFE exome AF: 0.598

Gnomad4 OTH exome AF: 0.544

GnomAD4 genome AF: 0.492 AC: 74821 AN: 152004 Hom.: 19992 Cov.: 32 AF XY: 0.490 AC XY: 36450 AN XY: 74312

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.504

Alfa AF: 0.533 Hom.: 2771

Bravo AF: 0.475

Asia WGS AF: 0.559 AC: 1946 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.033
DANN	Benign	0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1531137; hg19: chr3-46943028;