rs724448

Positions:

• chr3-46894244-A-C
• chr3-46894244-A-G
• chr3-46894244-A-T

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.178+235A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,932 control chromosomes in the GnomAD database, including 20,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (20216 hom., cov: 31)
• Consequence: PTH1R NM_000316.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.768

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 3-46894244-A-C is Benign according to our data. Variant chr3-46894244-A-C is described in ClinVar as [Benign]. Clinvar id is 1246255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTH1R	NM_000316.3	c.178+235A>C		intron_variant		ENST00000449590.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTH1R	ENST00000449590.6	c.178+235A>C		intron_variant		1	NM_000316.3	P1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75086 AN: 151814 Hom.: 20199 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.495 AC: 75139 AN: 151932 Hom.: 20216 Cov.: 31 AF XY: 0.493 AC XY: 36643 AN XY: 74258

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.505

Alfa AF: 0.529 Hom.: 3289

Bravo AF: 0.475

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	3.4
DANN	Benign	0.37

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: rs724448; hg19: chr3-46935734;