chr3-46888056-G-A

Position:

• chr3-46888056-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000316.3(PTH1R):​c.75+4422G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,106 control chromosomes in the GnomAD database, including 40,318 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (40318 hom., cov: 32)
• Consequence: PTH1R NM_000316.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTH1R	NM_000316.3	c.75+4422G>A		intron_variant		ENST00000449590.6	NP_000307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTH1R	ENST00000449590.6	c.75+4422G>A		intron_variant		1	NM_000316.3	ENSP00000402723.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109710 AN: 151988 Hom.: 40264 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.722 AC: 109820 AN: 152106 Hom.: 40318 Cov.: 32 AF XY: 0.717 AC XY: 53308 AN XY: 74338

Gnomad4 AFR AF: 0.853

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.665

Alfa AF: 0.664 Hom.: 43665

Bravo AF: 0.735

Asia WGS AF: 0.697 AC: 2428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.36

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: rs6442037; hg19: chr3-46929546;