rs2242116

Positions:

• chr3-46899626-A-G

Variant summary

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

The NM_000316.3(PTH1R):​c.988+170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,100 control chromosomes in the GnomAD database, including 22,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (22945 hom., cov: 33)
• Consequence: PTH1R NM_000316.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-46899626-A-G is Benign according to our data. Variant chr3-46899626-A-G is described in ClinVar as [Benign]. Clinvar id is 1180250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTH1R	NM_000316.3	c.988+170A>G		intron_variant		ENST00000449590.6	NP_000307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTH1R	ENST00000449590.6	c.988+170A>G		intron_variant		1	NM_000316.3	ENSP00000402723.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81511 AN: 151982 Hom.: 22916 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.550

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.536 AC: 81583 AN: 152100 Hom.: 22945 Cov.: 33 AF XY: 0.533 AC XY: 39635 AN XY: 74374

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.553

Alfa AF: 0.576 Hom.: 3229

Bravo AF: 0.523

Asia WGS AF: 0.582 AC: 2023 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 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.27
DANN	Benign	0.38

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: rs2242116; hg19: chr3-46941116;